133 results on '"Hideaki Kanazawa"'
Search Results
2. Assessment of Ebstein Severity in a 28-year-old Male with Multiple Large Ostium Secundum Atrial Septal Defects
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Masaki Kodaira, MD, Shigeo Okuda, MD, PhD, Naritaka Kimura, MD, PhD, Hideaki Kanazawa, MD, PhD, Hiroyuki Yamagishi, MD, PhD, and Masaki Ieda, MD, PhD
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Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Published
- 2024
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3. Upregulation of neuropeptide Y in cardiac sympathetic nerves induces stress (Takotsubo) cardiomyopathy
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Takahide Arai, Hideaki Kanazawa, Kensuke Kimura, Masahito Munakata, Hiroyuki Yamakawa, Ken Shinmura, Shinsuke Yuasa, Motoaki Sano, and Keiichi Fukuda
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neuropeptide Y ,cardiac sympathetic nervous ,stellate ganglion ,stress ,Takotsubo cardiomyopathy ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Substantial emotional or physical stress may lead to an imbalance in the brain, resulting in stress cardiomyopathy (SC) and transient left ventricular (LV) apical ballooning. Even though these conditions are severe, their precise underlying mechanisms remain unclear. Appropriate animal models are needed to elucidate the precise mechanisms. In this study, we established a new animal model of epilepsy-induced SC. The SC model showed an increased expression of the acute phase reaction protein, c-Fos, in the paraventricular hypothalamic nucleus (PVN), which is the sympathetic nerve center of the brain. Furthermore, we observed a significant upregulation of neuropeptide Y (NPY) expression in the left stellate ganglion (SG) and cardiac sympathetic nerves. NPY showed neither positive nor negative inotropic and chronotropic effects. On the contrary, NPY could interrupt β-adrenergic signaling in cardiomyocytes when exposure to NPY precedes exposure to noradrenaline. Moreover, its elimination in the left SG via siRNA treatment tended to reduce the incidence of SC. Thus, our results indicated that upstream sympathetic activation induced significant upregulation of NPY in the left SG and cardiac sympathetic nerves, resulting in cardiac dysfunctions like SC.
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- 2022
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4. The plasticity of cardiac sympathetic nerves and its clinical implication in cardiovascular disease
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Hideaki Kanazawa and Keiichi Fukuda
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heart failure ,cardiac sympathetic nerves ,parasympathetic nerves ,plasticity ,vagal nerve stimulation (VNS) ,cholinergic trans-differentiation ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
The heart is electrically and mechanically controlled by the autonomic nervous system, which consists of both the sympathetic and parasympathetic systems. It has been considered that the sympathetic and parasympathetic nerves regulate the cardiomyocytes’ performance independently; however, recent molecular biology approaches have provided a new concept to our understanding of the mechanisms controlling the diseased heart through the plasticity of the autonomic nervous system. Studies have found that cardiac sympathetic nerve fibers in hypertrophic ventricles strongly express an immature neuron marker and simultaneously cause deterioration of neuronal cellular function. This phenomenon was explained by the rejuvenation of cardiac sympathetic nerves. Moreover, heart failure and myocardial infarction have been shown to cause cholinergic trans-differentiation of cardiac sympathetic nerve fibers via gp130-signaling cytokines secreted from the failing myocardium, affecting cardiac performance and prognosis. This phenomenon is thought to be one of the adaptations that prevent the progression of heart disease. Recently, the concept of using device-based neuromodulation therapies to attenuate sympathetic activity and increase parasympathetic (vagal) activity to treat cardiovascular disease, including heart failure, was developed. Although several promising preclinical and pilot clinical studies using these strategies have been conducted, the results of clinical efficacy vary. In this review, we summarize the current literature on the plasticity of cardiac sympathetic nerves and propose potential new therapeutic targets for heart disease.
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- 2022
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5. Assessment of cardiac function in rat endovascular perforation model of subarachnoid hemorrhage; A model of subarachnoid hemorrhage-induced cardiac dysfunction
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Masahito Munakata, Hideaki Kanazawa, Kensuke Kimura, Takahide Arai, Hiroaki Sukegawa, and Keiichi Fukuda
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subarachnoid hemorrhage ,animal model ,cardiac dysfunction ,arrhythmia ,CXCL-1 chemokine ,CCL-2 ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Although the association between cardiac dysfunction and subarachnoid hemorrhage (SAH) has been recognized, its precise underlying mechanism remains unknown. Furthermore, no suitable animal models are available to study this association. Here, we established an appropriate animal model of SAH-induced cardiac dysfunction and elucidated its mechanism. In this rat model, contrast-enhanced computed tomography of the brain confirmed successful induction of SAH. Electrocardiography detected abnormalities in 55% of the experimental animals, while echocardiography indicated cardiac dysfunction in 30% of them. Further evaluation of left ventriculography confirmed cardiac dysfunction, which was transient and recovered over time. Additionally, in this SAH model, the expression of the acute phase reaction protein, proto-oncogene c-Fos increased in the paraventricular hypothalamic nucleus (PVN), the sympathetic nerve center of the brain. Polymerase chain reaction analysis revealed that the SAH model with cardiac dysfunction had higher levels of the macrophage-associated chemokine (C-X-C motif) ligand 1 (CXCL-1) and chemokine (C-C motif) ligand 2 (CCL-2) than the SAH model without cardiac dysfunction. Our results suggested that SAH caused inflammation and macrophage activation in the PVN, leading to sympathetic hyperexcitability that might cause cardiac dysfunction directly and indirectly. This animal model may represent a powerful tool to investigate the mechanisms of the brain-heart pathway.
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- 2022
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6. Incoordination during the pharyngeal phase in severe dysphagia due to lateral medullary syndrome
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Kenjiro Kunieda, Takafumi Sugi, Tomohisa Ohno, Akiko Nomoto, Takashi Shigematsu, Hideaki Kanazawa, and Ichiro Fujishima
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central pattern generator ,high‐resolution manometry ,incoordination ,lateral medullary syndrome ,upper esophageal sphincter ,Medicine ,Medicine (General) ,R5-920 - Abstract
Abstract One of the mechanisms of severe dysphagia due to lateral medullary syndrome may be a reversed pressure gradient caused by incoordination of pharyngeal contractility and UES opening during swallowing.
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- 2021
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7. Percutaneous Patent Foramen Ovale Closure in a Patient With Anomalous Aortic Origin of the Left Coronary ArteryNovel Teaching Points
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Shiro Miura, MD, MSc, Takehiro Yamashita, MD, PhD, Hideaki Kanazawa, MD, PhD, Hidehiko Hara, MD, PhD, and Jonathan M. Tobis, MD
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Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Published
- 2022
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8. The Present State and Future Perspectives of Cardiac Regenerative Therapy Using Human Pluripotent Stem Cells
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Yusuke Soma, Yuika Morita, Yoshikazu Kishino, Hideaki Kanazawa, Keiichi Fukuda, and Shugo Tohyama
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regenerative therapy ,embryonic stem cell (ES cells) ,induced pluripotent stem cell (iPS cell) (iPSC) ,stem cell metabolism ,heart failure ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
The number of patients with heart failure (HF) is increasing with aging in our society worldwide. Patients with HF who are resistant to medication and device therapy are candidates for heart transplantation (HT). However, the shortage of donor hearts is a serious issue. As an alternative to HT, cardiac regenerative therapy using human pluripotent stem cells (hPSCs), such as human embryonic stem cells and induced pluripotent stem cells, is expected to be realized. Differentiation of hPSCs into cardiomyocytes (CMs) is facilitated by mimicking normal heart development. To prevent tumorigenesis after transplantation, it is important to eliminate non-CMs, including residual hPSCs, and select only CMs. Among many CM selection systems, metabolic selection based on the differences in metabolism between CMs and non-CMs is favorable in terms of cost and efficacy. Large-scale culture systems have been developed because a large number of hPSC-derived CMs (hPSC-CMs) are required for transplantation in clinical settings. In large animal models, hPSC-CMs transplanted into the myocardium improved cardiac function in a myocardial infarction model. Although post-transplantation arrhythmia and immune rejection remain problems, their mechanisms and solutions are under investigation. In this manner, the problems of cardiac regenerative therapy are being solved individually. Thus, cardiac regenerative therapy with hPSC-CMs is expected to become a safe and effective treatment for HF in the near future. In this review, we describe previous studies related to hPSC-CMs and discuss the future perspectives of cardiac regenerative therapy using hPSC-CMs.
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- 2021
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9. Tryptophan Metabolism Regulates Proliferative Capacity of Human Pluripotent Stem Cells
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Shota Someya, Shugo Tohyama, Kotaro Kameda, Sho Tanosaki, Yuika Morita, Kazunori Sasaki, Moon-Il Kang, Yoshikazu Kishino, Marina Okada, Hidenori Tani, Yusuke Soma, Kazuaki Nakajima, Tomohiko Umei, Otoya Sekine, Taijun Moriwaki, Hideaki Kanazawa, Eiji Kobayashi, Jun Fujita, and Keiichi Fukuda
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Cell Biology ,Metabolomics ,Stem Cell Research ,Science - Abstract
Summary: Human pluripotent stem cells (hPSCs) have a unique metabolic signature for maintenance of pluripotency, self-renewal, and survival. Although hPSCs could be potentially used in regenerative medicine, the prohibitive cost associated with large-scale cell culture presents a major barrier to the clinical application of hPSC. Moreover, without a fully characterized metabolic signature, hPSC culture conditions are not optimized. Here, we performed detailed amino acid profiling and found that tryptophan (TRP) plays a key role in the proliferation with maintenance of pluripotency. In addition, metabolome analyses revealed that intra- and extracellular kynurenine (KYN) is decreased under TRP-supplemented conditions, whereas N-formylkynurenine (NFK), the upstream metabolite of KYN, is increased thereby contributing to proliferation promotion. Taken together, we demonstrate that TRP is indispensable for survival and proliferation of hPSCs. A deeper understanding of TRP metabolism will enable cost-effective large-scale production of hPSCs, leading to advances in regenerative medicine.
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- 2021
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10. Fatty Acid Synthesis Is Indispensable for Survival of Human Pluripotent Stem Cells
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Sho Tanosaki, Shugo Tohyama, Jun Fujita, Shota Someya, Takako Hishiki, Tomomi Matsuura, Hiroki Nakanishi, Takayo Ohto-Nakanishi, Tomohiko Akiyama, Yuika Morita, Yoshikazu Kishino, Marina Okada, Hidenori Tani, Yusuke Soma, Kazuaki Nakajima, Hideaki Kanazawa, Masahiro Sugimoto, Minoru S.H. Ko, Makoto Suematsu, and Keiichi Fukuda
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Biological Sciences ,Cell Biology ,Stem Cells Research ,Proteomics ,Metabolomics ,Metabolic Flux Analysis ,Science - Abstract
Summary: The role of lipid metabolism in human pluripotent stem cells (hPSCs) is poorly understood. We have used large-scale targeted proteomics to demonstrate that undifferentiated hPSCs express different fatty acid (FA) biosynthesis-related enzymes, including ATP citrate lyase and FA synthase (FASN), than those expressed in hPSC-derived cardiomyocytes (hPSC-CMs). Detailed lipid profiling revealed that inhibition of FASN resulted in significant reduction of sphingolipids and phosphatidylcholine (PC); moreover, we found that PC was the key metabolite for cell survival in hPSCs. Inhibition of FASN induced cell death in undifferentiated hPSCs via mitochondria-mediated apoptosis; however, it did not affect cell survival in hPSC-CMs, neurons, or hepatocytes as there was no significant reduction of PC. Furthermore, we did not observe tumor formation following transplantation of FASN inhibitor-treated cells. Our findings demonstrate the importance of de novo FA synthesis in the survival of undifferentiated hPSCs and suggest applications for FASN inhibition in regenerative medicine.
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- 2020
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11. Efficient Large-Scale 2D Culture System for Human Induced Pluripotent Stem Cells and Differentiated Cardiomyocytes
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Shugo Tohyama, Jun Fujita, Chihana Fujita, Miho Yamaguchi, Sayaka Kanaami, Rei Ohno, Kazuho Sakamoto, Masami Kodama, Junko Kurokawa, Hideaki Kanazawa, Tomohisa Seki, Yoshikazu Kishino, Marina Okada, Kazuaki Nakajima, Sho Tanosaki, Shota Someya, Akinori Hirano, Shinji Kawaguchi, Eiji Kobayashi, and Keiichi Fukuda
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Medicine (General) ,R5-920 ,Biology (General) ,QH301-705.5 - Abstract
Summary: Cardiac regenerative therapies utilizing human induced pluripotent stem cells (hiPSCs) are hampered by ineffective large-scale culture. hiPSCs were cultured in multilayer culture plates (CPs) with active gas ventilation (AGV), resulting in stable proliferation and pluripotency. Seeding of 1 × 106 hiPSCs per layer yielded 7.2 × 108 hiPSCs in 4-layer CPs and 1.7 × 109 hiPSCs in 10-layer CPs with pluripotency. hiPSCs were sequentially differentiated into cardiomyocytes (CMs) in a two-dimensional (2D) differentiation protocol. The efficiency of cardiac differentiation using 10-layer CPs with AGV was 66%–87%. Approximately 6.2–7.0 × 108 cells (4-layer) and 1.5–2.8 × 109 cells (10-layer) were obtained with AGV. After metabolic purification with glucose- and glutamine-depleted and lactate-supplemented media, a massive amount of purified CMs was prepared. Here, we present a scalable 2D culture system using multilayer CPs with AGV for hiPSC-derived CMs, which will facilitate clinical applications for severe heart failure in the near future. : In this article, Fujita and colleagues show that human induced pluripotent stem cells (hiPSCs) and hiPSC-derived cardiomyocytes (hiPSC-CMs) are stably and efficiently produced using multilayer culture plates with an active gas ventilation system because of stable CO2 and O2 concentration in culture media. Large numbers of obtained hiPSC-CMs are metabolically purified under glucose- and glutamine-depleted and lactate-supplemented conditions. Keywords: iPSCs, regenerative medicine, cardiomyocytes, purification, large scale, 2D culture
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- 2017
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12. Durable Benefits of Cellular Postconditioning: Long‐Term Effects of Allogeneic Cardiosphere‐Derived Cells Infused After Reperfusion in Pigs with Acute Myocardial Infarction
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Hideaki Kanazawa, Eleni Tseliou, James F. Dawkins, Geoffrey De Couto, Romain Gallet, Konstantinos Malliaras, Kristine Yee, Michelle Kreke, Ileana Valle, Rachel R. Smith, Ryan C. Middleton, Chak‐Sum Ho, Rohan Dharmakumar, Debiao Li, Raj R. Makkar, Keiichi Fukuda, Linda Marbán, and Eduardo Marbán
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allogeneic transplantation ,cardioprotective effect ,cardiosphere‐derived cells ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
BackgroundInfusion of allogeneic cardiosphere‐derived cells (allo‐CDCs) postreperfusion elicits cardioprotective cellular postconditioning in pigs with acute myocardial infarction. However, the long‐term effects of allo‐CDCs have not been assessed. We performed a placebo‐controlled pivotal study for long‐term evaluation, as well as shorter‐term mechanistic studies. Methods and ResultsMinipigs underwent 1.5‐hour mid‐left anterior descending balloon occlusion followed by reperfusion and were randomized to receive intracoronary allo‐CDCs or vehicle 30 minutes postreperfusion. Left ventriculography (LVG) demonstrated preserved ejection fraction (EF) and attenuation of LV remodeling in CDC‐treated pigs. Pigs underwent cardiac magnetic resonance imaging (MRI) and LVG 1 hour and 8 weeks after therapy to evaluate efficacy. MRI showed improvement of EF and attenuation of LV remodeling immediately after allo‐CDC infusion. In addition, allo‐CDCs improved regional function and decreased hypertrophy 2 months post‐treatment. Histological analysis revealed increased myocardial salvage index, enhanced vascularity, sustained reductions in infarct size/area at risk and scar transmurality, and attenuation of collagen deposition in the infarct zone of allo‐CDC‐treated pigs at 2 months. Allo‐CDCs did not evoke lymphohistiocytic infiltration or systemic humoral memory response. Short‐term experiments designed to probe mechanism revealed antiapoptotic effects of allo‐CDCs on cardiomyocytes and increases in cytoprotective macrophages, but no increase in overall inflammatory cell infiltration 2 hours after cell therapy. ConclusionsAllo‐CDC infusion postreperfusion is safe, improves cardiac function, and attenuates scar size and remodeling. The favorable effects persist for at least 2 months after therapy. Thus, cellular postconditioning confers not only acute cardioprotection, but also lasting structural and functional benefits.
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- 2016
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13. Widespread Myocardial Delivery of Heart-Derived Stem Cells by Nonocclusive Triple-Vessel Intracoronary Infusion in Porcine Ischemic Cardiomyopathy: Superior Attenuation of Adverse Remodeling Documented by Magnetic Resonance Imaging and Histology.
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Eleni Tseliou, Hideaki Kanazawa, James Dawkins, Romain Gallet, Michelle Kreke, Rachel Smith, Ryan Middleton, Jackelyn Valle, Linda Marbán, Saibal Kar, Rajendra Makkar, and Eduardo Marbán
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Medicine ,Science - Abstract
Single-vessel, intracoronary infusion of stem cells under stop-flow conditions has proven safe but achieves only limited myocardial coverage. Continuous flow intracoronary delivery to one or more coronary vessels may achieve broader coverage for treating cardiomyopathy, but has not been investigated. Using nonocclusive coronary guiding catheters, we infused allogeneic cardiosphere-derived cells (CDCs) either in a single vessel or sequentially in all three coronary arteries in porcine ischemic cardiomyopathy and used magnetic resonance imaging (MRI) to assess structural and physiological outcomes. Vehicle-infused animals served as controls. Single-vessel stop-flow and continuous-flow intracoronary infusion revealed equivalent effects on scar size and function. Sequential infusion into each of the three major coronary vessels under stop-flow or continuous-flow conditions revealed equal efficacy, but less elevation of necrotic biomarkers with continuous-flow delivery. In addition, multi-vessel delivery resulted in enhanced global and regional tissue function compared to a triple-vessel placebo-treated group. The functional benefits after global cell infusion were accompanied histologically by minimal inflammatory cellular infiltration, attenuated regional fibrosis and enhanced vessel density in the heart. Sequential multi-vessel non-occlusive delivery of CDCs is safe and provides enhanced preservation of left ventricular function and structure. The current findings provide preclinical validation of the delivery method currently undergoing clinical testing in the Dilated cardiomYopathy iNtervention With Allogeneic MyocardIally-regenerative Cells (DYNAMIC) trial of CDCs in heart failure patients.
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- 2016
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14. Gelatin Hydrogel Enhances the Engraftment of Transplanted Cardiomyocytes and Angiogenesis to Ameliorate Cardiac Function after Myocardial Infarction.
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Kazuaki Nakajima, Jun Fujita, Makoto Matsui, Shugo Tohyama, Noriko Tamura, Hideaki Kanazawa, Tomohisa Seki, Yoshikazu Kishino, Akinori Hirano, Marina Okada, Ryota Tabei, Motoaki Sano, Shinya Goto, Yasuhiko Tabata, and Keiichi Fukuda
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Medicine ,Science - Abstract
Cell transplantation therapy will mean a breakthrough in resolving the donor shortage in cardiac transplantation. Cardiomyocyte (CM) transplantation, however, has been relatively inefficient in restoring cardiac function after myocardial infarction (MI) due to low engraftment of transplanted CM. In order to ameliorate engraftment of CM, the novel transplantation strategy must be invented. Gelatin hydrogel (GH) is a biodegradable water-soluble polymer gel. Gelatin is made of collagen. Although we observed that collagen strongly induced the aggregation of platelets to potentially cause coronary microembolization, GH did not enhance thrombogenicity. Therefore, GH is a suitable biomaterial in the cell therapy after heart failure. To assess the effect of GH on the improvement of cardiac function, fetal rat CM (5×10(6) or 1x10(6) cells) were transplanted with GH (10 mg/ml) to infarcted hearts. We compared this group with sham operated rats, CM in phosphate buffered saline (PBS), only PBS, and only GH-transplanted groups. Three weeks after transplantation, cardiac function was evaluated by echocardiography. The echocardiography confirmed that transplantation of 5×10(6) CM with GH significantly improved cardiac systolic function, compared with the CM+PBS group (fractional area change: 75.1±3.4% vs. 60.7±5.9%, p
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- 2015
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15. The Prevalence of Clinically Significant Ischemia in Patients Undergoing Percutaneous Coronary Intervention: A Report from the Multicenter Registry.
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Jun Fujita, Shun Kohsaka, Ikuko Ueda, Taku Inohara, Yuichiro Maekawa, Akio Kawamura, Hideaki Kanazawa, Kentaro Hayashida, Ryota Tabei, Shugo Tohyama, Tomohisa Seki, Masahiro Suzuki, Motoaki Sano, and Keiichi Fukuda
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Medicine ,Science - Abstract
Myocardial perfusion scintigraphy (MPS) plays an important role in the evaluation and quantification of myocardial ischemia, and those with significant ischemia (SI) benefit most from revascularization procedures. This study aimed to identify the clinical factors and anatomical features associated with SI in patients with stable ischemic heart disease (SIHD).Data were analyzed from 4197 SIHD patients undergoing percutaneous coronary intervention (PCI). Ischemia was based on MPS findings prior to PCI, with SI defined as an ischemic region of more than 10% of the total left ventricular area. Logistic regression analysis was performed to identify any clinical factors associated with SI. MPS was used to evaluate 1070 (25.5%) patients pre-procedurally. Patients with a history of heart failure, stroke, or anginal symptoms with Canadian Cardiovascular Society class 2 or more were more likely to have SI (odds ratio [OR] 1.63, p = 0.025, OR: 1.85, p = 0.009, and OR: 1.49, p = 0.003, respectively). When angiographic variables were considered, a proximal left anterior descending artery (pLAD) lesion was the sole factor associated with SI (OR: 1.45, p = 0.012). Importantly, those with SI had more in-hospital complications (p = 0.006), most notably post-PCI infarcts (p = 0.008).Patients' background data, such as stronger anginal symptoms or a pLAD lesion, were associated with SI. Patients with SI must be treated with PCI to improve their long-term prognosis; however, procedure-related complications happen more frequently in SI patients than in non-SI patients. Physicians must give their full attention when performing the PCI procedure in SI patients to minimize their complication rate.
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- 2015
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16. Allogeneic cardiospheres delivered via percutaneous transendocardial injection increase viable myocardium, decrease scar size, and attenuate cardiac dilatation in porcine ischemic cardiomyopathy.
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Kristine Yee, Konstantinos Malliaras, Hideaki Kanazawa, Eleni Tseliou, Ke Cheng, Daniel J Luthringer, Chak-Sum Ho, Kentaro Takayama, Naoto Minamino, James F Dawkins, Supurna Chowdhury, Doan Trang Duong, Jeffrey Seinfeld, Ryan C Middleton, Rohan Dharmakumar, Debiao Li, Linda Marbán, Raj R Makkar, and Eduardo Marbán
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Medicine ,Science - Abstract
BackgroundEpicardial injection of heart-derived cell products is safe and effective post-myocardial infarction (MI), but clinically-translatable transendocardial injection has never been evaluated. We sought to assess the feasibility, safety and efficacy of percutaneous transendocardial injection of heart-derived cells in porcine chronic ischemic cardiomyopathy.Methods and resultsWe studied a total of 89 minipigs; 63 completed the specified protocols. After NOGA-guided transendocardial injection, we quantified engraftment of escalating doses of allogeneic cardiospheres or cardiosphere-derived cells in minipigs (n = 22) post-MI. Next, a dose-ranging, blinded, randomized, placebo-controlled ("dose optimization") study of transendocardial injection of the better-engrafting product was performed in infarcted minipigs (n = 16). Finally, the superior product and dose (150 million cardiospheres) were tested in a blinded, randomized, placebo-controlled ("pivotal") study (n = 22). Contrast-enhanced cardiac MRI revealed that all cardiosphere doses preserved systolic function and attenuated remodeling. The maximum feasible dose (150 million cells) was most effective in reducing scar size, increasing viable myocardium and improving ejection fraction. In the pivotal study, eight weeks post-injection, histopathology demonstrated no excess inflammation, and no myocyte hypertrophy, in treated minipigs versus controls. No alloreactive donor-specific antibodies developed over time. MRI showed reduced scar size, increased viable mass, and attenuation of cardiac dilatation with no effect on ejection fraction in the treated group compared to placebo.ConclusionsDose-optimized injection of allogeneic cardiospheres is safe, decreases scar size, increases viable myocardium, and attenuates cardiac dilatation in porcine chronic ischemic cardiomyopathy. The decreases in scar size, mirrored by increases in viable myocardium, are consistent with therapeutic regeneration.
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- 2014
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17. Derivation of transgene-free human induced pluripotent stem cells from human peripheral T cells in defined culture conditions.
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Yoshikazu Kishino, Tomohisa Seki, Jun Fujita, Shinsuke Yuasa, Shugo Tohyama, Akira Kunitomi, Ryota Tabei, Kazuaki Nakajima, Marina Okada, Akinori Hirano, Hideaki Kanazawa, and Keiichi Fukuda
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Medicine ,Science - Abstract
Recently, induced pluripotent stem cells (iPSCs) were established as promising cell sources for revolutionary regenerative therapies. The initial culture system used for iPSC generation needed fetal calf serum in the culture medium and mouse embryonic fibroblast as a feeder layer, both of which could possibly transfer unknown exogenous antigens and pathogens into the iPSC population. Therefore, the development of culture systems designed to minimize such potential risks has become increasingly vital for future applications of iPSCs for clinical use. On another front, although donor cell types for generating iPSCs are wide-ranging, T cells have attracted attention as unique cell sources for iPSCs generation because T cell-derived iPSCs (TiPSCs) have a unique monoclonal T cell receptor genomic rearrangement that enables their differentiation into antigen-specific T cells, which can be applied to novel immunotherapies. In the present study, we generated transgene-free human TiPSCs using a combination of activated human T cells and Sendai virus under defined culture conditions. These TiPSCs expressed pluripotent markers by quantitative PCR and immunostaining, had a normal karyotype, and were capable of differentiating into cells from all three germ layers. This method of TiPSCs generation is more suitable for the therapeutic application of iPSC technology because it lowers the risks associated with the presence of undefined, animal-derived feeder cells and serum. Therefore this work will lead to establishment of safer iPSCs and extended clinical application.
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- 2014
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18. Cardiac Regenerative Therapy Using Human Pluripotent Stem Cells for Heart Failure: A State-of-the-Art Review
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YOSHIKAZU KISHINO, SHUGO TOHYAMA, YUIKA MORITA, YUSUKE SOMA, HIDENORI TANI, MARINA OKADA, HIDEAKI KANAZAWA, and KEIICHI FUKUDA
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Cardiology and Cardiovascular Medicine - Published
- 2023
19. Intracardiac Echocardiography Guidance for Percutaneous Transcatheter Closure of Atrial Septal Defects ― Nationwide Registry Data Analysis ―
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Yasuhiro Tanabe, Mitsuyoshi Takahara, Shun Kohsaka, Toshiro Shinke, Itaru Takamisawa, Tetsuya Amano, Hideaki Kanazawa, Tomomi Suzuki, Shingo Kuwata, Yuki Ishibashi, Yoshihiro J. Akashi, and Yuji Ikari
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General Medicine ,Cardiology and Cardiovascular Medicine - Published
- 2023
20. Iatrogenic Atrial Septal Defect Requiring Transcatheter Closure Following Transcatheter Mitral Valve Repair
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Yoichi, Takaya, Teiji, Akagi, Hidehiko, Hara, Hideaki, Kanazawa, Yuji, Ikari, Akihiro, Isotani, Shinichi, Shirai, Shunsuke, Kubo, Takao, Morikawa, Toru, Naganuma, Mike, Saji, Shingo, Kuwata, Go, Hiasa, Yusuke, Watanabe, Masahiro, Yamawaki, Masao, Imai, Takashi, Matsumoto, Masanori, Yamamoto, Tsutomu, Murakami, Masahiko, Asami, Isamu, Mizote, Tsukasa, Okai, Hiroki, Bota, and Hiroshi, Ito
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Heart Failure ,Cardiac Catheterization ,Treatment Outcome ,Iatrogenic Disease ,Humans ,Mitral Valve ,Mitral Valve Insufficiency ,General Medicine ,Hypoxia ,Cardiology and Cardiovascular Medicine ,Heart Septal Defects, Atrial - Abstract
Transcatheter mitral valve repair with the MitraClip system has been established in selected high-risk patients. The MitraClip procedure results in a relatively large iatrogenic atrial septal defect (iASD). This study aimed to investigate the prevalence and clinical course of iASD requiring transcatheter closure following the MitraClip procedure.Methods and Results: This study was conducted at all 59 institutions that perform transcatheter mitral valve repair with the MitraClip system in Japan. The data of patients on whom transcatheter iASD closure was performed were collected. Of the 2,722 patients who underwent the MitraClip procedure, 30 (1%) required transcatheter iASD closure. The maximum iASD size was 9±4 mm (range, 3-18 mm). The common clinical course of transcatheter iASD closure was hypoxemia with right-to-left shunt or right-sided heart failure with left-to-right shunt. Of the 30 patients, 22 (73%) required transcatheter closure within 24 h following the MitraClip procedure, including 12 with hypoxemia and 5 with right-sided heart failure complicated with cardiogenic shock. Of the 5 patients, 2 required mechanical circulatory support devices. Twenty-one patients immediately underwent transcatheter iASD closure, and hemodynamic deteriorations were resolved; however, 1 patient died without having undergone transcatheter closure.Transcatheter iASD closure was required in 1% of patients who underwent the MitraClip procedure. Many of these patients immediately underwent transcatheter iASD closure because of hypoxemia with right-to-left shunt or right-sided heart failure with left-to-right shunt.
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- 2022
21. Reduction of Atrial Septal Defect Size After Catheter Ablation for Atrial Tachyarrhythmia and Its Predictive Factors
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Mai Kimura, Keitaro Shinada, Kotaro Miura, Jin Endo, Hikaru Tsuruta, Yuji Itabashi, Yoshinori Katsumata, Takehiro Kimura, Seiji Takatsuki, Keiichi Fukuda, and Hideaki Kanazawa
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- 2022
22. Impaired Left Atrial Function in Patients with Atrial Septal Defect and History of Atrial Fibrillation
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Manabu Nitta, Makoto Kaneko, Sayuri Shimizu, Hideaki Kanazawa, Yuji Itabashi, Kotaro Miura, Mike Saji, Itaru Takamisawa, Morimasa Takayama, Shintaro Nakano, Saki Hasegawa-Tamba, and Shinichiro Ueda
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General Medicine ,Cardiology and Cardiovascular Medicine - Published
- 2022
23. Transcatheter retrieval of atrial septal defect and patent ductus arteriosus occluder: a guidance for device retrieval based on comprehensive bench tests
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Takanari Fujii, Hisashi Sugiyama, Hideaki Kanazawa, Hidehiko Hara, Jun Muneuchi, and Satoshi Yazaki
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Pediatrics, Perinatology and Child Health ,General Medicine ,Cardiology and Cardiovascular Medicine - Abstract
Objectives: The aim of this study is to establish a guidance for device retrieval based on comprehensive bench tests. Background: Device embolisation remains a major complication in transcatheter closure of atrial septal defect and patent ductus arteriosus. Although percutaneous retrieval is feasible in the majority of cases, surgical retrieval may be required in complicated circumstances. However, the methods of transcatheter device retrieval have not been completely established. Methods: Bench tests of device retrieval were performed to verify the appropriate retrieval method according to device type/size. The devices used for testing were Amplatzer Septal Occluder (Abbott, Chicago, IL, United States of America), Figulla Flex II (Occlutech GmbH, Jena, Germany), Amplatzer Duct Occluder-I (Abbott), Amplatzer Duct Occluder-II (Abbott), and Amplatzer Vascular Plug-II (Abbott). The retrieval equipment constituted diagnostic catheters (multipurpose catheter and right Judkins catheter, 4-Fr or 5-Fr, Gadelius Medical, Tokyo, Japan), delivery sheath and cables for each device, Amplatz goose neck snares (Medtronic, Minneapolis, MN, United States of America), OSYPKA CATCHER (Osypka ag, Rheinfelden-Herten, Germany), and OSYPKA LASSOS (Osypka). We investigated the retrieval equipment and sheath sizes required for a successful retrieval procedure for variously sized devices. Results: For patent ductus arteriosus devices, the type of snare and the snaring position are considered important. For atrial septal defect devices, simple snare capture or a double-snare technique with a sufficiently large sheath is effective. Special care should be taken when using the OSYPKA CATCHER for device retrieval. Conclusions: The results of this study may assist in the selection of both capture devices and a retrieval sheath or a catheter for complete retrieval.
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- 2022
24. Deep Learning-Based Model Detects Atrial Septal Defectsfrom Electrocardiography: A Multicenter Study
- Author
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Kotaro Miura, Shinichi Goto, Hiroshi Miyama, Mai Kimura, Hideaki Kanazawa, Masahiro Hashimoto, Sayuki Kobayashi, Shiro Nakahara, Tetsuya Ishikawa, Isao Taguchi, Motoaki Sano, Kazuki Sato, Keiichi Fukuda, Yuji Itabashi, and Yoshinori Katsumata
- Published
- 2023
25. Production of functional cardiomyocytes and cardiac tissue from human induced pluripotent stem cells for regenerative therapy
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Hideaki Kanazawa, Yoshikazu Kishino, Hidenori Tani, Keiichi Fukuda, and Shugo Tohyama
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Heart Failure ,Heart transplantation ,education.field_of_study ,business.industry ,medicine.medical_treatment ,Lactate dehydrogenase A ,Induced Pluripotent Stem Cells ,Cell Differentiation ,medicine.disease ,Bioinformatics ,Regenerative medicine ,Embryonic stem cell ,Transplantation ,health services administration ,Heart failure ,Humans ,Medicine ,Myocytes, Cardiac ,Human Induced Pluripotent Stem Cells ,Cardiology and Cardiovascular Medicine ,business ,education ,Induced pluripotent stem cell ,Molecular Biology ,health care economics and organizations - Abstract
The emergence of human induced pluripotent stem cells (hiPSCs) has revealed the potential for curing end-stage heart failure. Indeed, transplantation of hiPSC-derived cardiomyocytes (hiPSC-CMs) may have applications as a replacement for heart transplantation and conventional regenerative therapies. However, there are several challenges that still must be overcome for clinical applications, including large-scale production of hiPSCs and hiPSC-CMs, elimination of residual hiPSCs, purification of hiPSC-CMs, maturation of hiPSC-CMs, efficient engraftment of transplanted hiPSC-CMs, development of an injection device, and avoidance of post-transplant arrhythmia and immunological rejection. Thus, we developed several technologies based on understanding of the metabolic profiles of hiPSCs and hiPSC derivatives. In this review, we outline how to overcome these hurdles to realize the transplantation of hiPSC-CMs in patients with heart failure and introduce cutting-edge findings and perspectives for future regenerative therapy.
- Published
- 2022
26. Intracardiac echocardiography guidance for percutaneous transcatheter closure of atrial septal defects: A nationwide registry data analysis
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Yasuhiro Tanabe, Mitsuyoshi Takahara, Shun Kohsaka, Toshiro Shinke, Itaru Takamisawa, Tetsuya Amano, Hideaki Kanazawa, Tomomi Suzuki, Shingo Kuwata, Yuki Ishibashi, Yoshihiro J Akashi, and Yuji Ikari
- Abstract
The authors have withdrawn their manuscript because they decided to modify their analysis because of how the imaging devices are employed in the real-world practice in Japan. Instead of simply comparing ICE vs. TEE patients, they decided that 3-way comparison comparing patients that underwent ASD closure with ICE alone vs. TEE alone vs Both Modalities is more practical and send clinically useful messages to the practicing physicians. Since it is highly likely that the above analysis will alter subsequent conclusions, the authors decided to withdraw the present version of their manuscript. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.
- Published
- 2022
27. Heart-derived collagen promotes maturation of engineered heart tissue
- Author
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Hidenori Tani, Eiji Kobayashi, Shinomi Yagi, Keisuke Tanaka, Kotaro Kameda-Haga, Shinsuke Shibata, Nobuko Moritoki, Kaworu Takatsuna, Taijun Moriwaki, Otoya Sekine, Tomohiko Umei, Yuika Morita, Yusuke Soma, Yoshikazu Kishino, Hideaki Kanazawa, Jun Fujita, Shunji Hattori, Keiichi Fukuda, and Shugo Tohyama
- Subjects
Biomaterials ,Mechanics of Materials ,Biophysics ,Ceramics and Composites ,Bioengineering - Published
- 2023
28. Incoordination during the pharyngeal phase in severe dysphagia due to lateral medullary syndrome
- Author
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Ichiro Fujishima, Takashi Shigematsu, Hideaki Kanazawa, Akiko Nomoto, Takafumi Sugi, Kenjiro Kunieda, and Tomohisa Ohno
- Subjects
lateral medullary syndrome ,Medullary cavity ,Pharyngeal phase ,lcsh:Medicine ,Case Report ,Case Reports ,macromolecular substances ,030204 cardiovascular system & hematology ,Contractility ,03 medical and health sciences ,0302 clinical medicine ,Swallowing ,Severe dysphagia ,otorhinolaryngologic diseases ,Medicine ,High resolution manometry ,lcsh:R5-920 ,Lateral medullary syndrome ,incoordination ,business.industry ,musculoskeletal, neural, and ocular physiology ,lcsh:R ,digestive, oral, and skin physiology ,Central pattern generator ,General Medicine ,Anatomy ,medicine.disease ,central pattern generator ,Upper esophageal sphincter ,nervous system ,high‐resolution manometry ,030220 oncology & carcinogenesis ,lcsh:Medicine (General) ,business ,upper esophageal sphincter - Abstract
One of the mechanisms of severe dysphagia due to lateral medullary syndrome may be a reversed pressure gradient caused by incoordination of pharyngeal contractility and UES opening during swallowing.
- Published
- 2021
29. Intramyocardial Transplantation of Human iPS Cell–Derived Cardiac Spheroids Improves Cardiac Function in Heart Failure Animals
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Ryota Tabei, Yujiro Kawai, Kazuaki Nakajima, Satoshi Kunita, Shota Someya, Jun Fujita, Hidenori Tani, Keiichi Fukuda, Yoshikazu Kishino, Hideaki Kanazawa, Shugo Tohyama, Takumi Teratani, Akira Ito, Noriko Handa, Akinori Hirano, Rei Shibata, Sho Tanosaki, Eiji Kobayashi, Shuji Hishikawa, Marina Okada, Hideyuki Shimizu, Masataka Yamazaki, Shigeo Okuda, Yoshitake Yamada, Yusuke Soma, Yasuhiko Tabata, Yuika Morita, Shinji Kawaguchi, and Toyoaki Murohara
- Subjects
0301 basic medicine ,Cardiac function curve ,medicine.medical_specialty ,LVEDV, left ventricular end-diastolic volume ,Cell ,heart failure ,cardiomyocyte ,030204 cardiovascular system & hematology ,HF, heart failure ,human iPS cells ,03 medical and health sciences ,0302 clinical medicine ,sCM, single cardiomyocyte ,CMR, cardiac magnetic resonance ,Internal medicine ,hiPSC, human induced pluripotent stem cell ,medicine ,dp/dtmax, maximum rate of left ventricular pressure rise ,EF, ejection fraction ,CM, cardiomyocyte ,Induced pluripotent stem cell ,cell transplantation ,LV, left ventricular ,Ejection fraction ,business.industry ,Spheroid ,medicine.disease ,FAC, fractional area change ,VEGF, vascular endothelial growth factor ,Transplantation ,030104 developmental biology ,medicine.anatomical_structure ,GH, gelatin hydrogel ,hPSC, human pluripotent stem cell ,cardiac spheroids ,Heart failure ,Cardiology ,LVESV, left ventricular end-systolic volume ,ECG, electrocardiogram ,Teratoma ,Preclinical Research ,Cardiology and Cardiovascular Medicine ,business ,CS, cardiac spheroid - Abstract
Visual Abstract, Highlights • hiPSCs are differentiated into CMs with large-scale 2-dimensional culture system, and refined by metabolic purification. • hiPSC-derived CMs are developed into CSs in special microwell plates. • Intramyocardial transplantation of CSs and GH improves cardiac function in small and large animal models. • Engraftment of CMs and angiogenesis are mechanisms for improvement of cardiac function. • Intramyocardial transplantation of CSs with a transplant injection device is a safe, effective, and feasible strategy for the treatment of HF., Summary The severe shortage of donor hearts hampered the cardiac transplantation to patients with advanced heart failure. Therefore, cardiac regenerative therapies are eagerly awaited as a substitution. Human induced pluripotent stem cells (hiPSCs) are realistic cell source for regenerative cardiomyocytes. The hiPSC-derived cardiomyocytes are highly expected to help the recovery of heart. Avoidance of teratoma formation and large-scale culture of cardiomyocytes are definitely necessary for clinical setting. The combination of pure cardiac spheroids and gelatin hydrogel succeeded to recover reduced ejection fraction. The feasible transplantation strategy including transplantation device for regenerative cardiomyocytes are established in this study.
- Published
- 2021
30. Evaluation of a palatal lift prosthesis with a flexible lift in a lower cranial nerve palsy patient with dysphagia using high-resolution manometry: A case report
- Author
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Shunsuke Minakuchi, Akiko Nomoto, Akio Shimizu, Kyoko Hojo, Kenjiro Kunieda, Ichiro Fujishima, Hideaki Kanazawa, Tomohisa Ohno, and Takashi Shigematsu
- Subjects
Palatal lift prosthesis ,medicine.medical_specialty ,Manometry ,0206 medical engineering ,chemical and pharmacologic phenomena ,02 engineering and technology ,03 medical and health sciences ,Dysarthria ,0302 clinical medicine ,Swallowing ,immune system diseases ,otorhinolaryngologic diseases ,medicine ,Humans ,Dentistry (miscellaneous) ,Pharyngeal Residue ,High resolution manometry ,Dental Implants ,business.industry ,030206 dentistry ,Esophageal Sphincter, Upper ,Hypernasal speech ,medicine.disease ,020601 biomedical engineering ,Dysphagia ,Cranial Nerve Diseases ,nervous system diseases ,Surgery ,Cranial Nerve Injury ,lipids (amino acids, peptides, and proteins) ,Oral Surgery ,medicine.symptom ,Deglutition Disorders ,business - Abstract
Patient Palatal lift prostheses (PLPs) are used for dysarthria caused by velopharyngeal incompetence (VPI) and improving hypernasal speech. In this case, we used a PLP with a flexible lift (f-PLP) in a patient with dysphagia associated with VPI due to right-sided cranial nerve injuries after a skull base surgery. We examined its efficacy in swallowing biomechanics and swallowing function using high-resolution manometry (HRM) and videofluoroscopic examination of swallowing (VF). The patient felt that it was easier to swallow with f-PLP. Furthermore, VF indicated that the pharyngeal residue with f-PLP was less than without it. HRM showed that velopharyngeal pressure and intrabolus pressure (IBP) with f-PLP were higher than those without it. Additionally, the upper esophageal sphincter (UES) relaxation time and UES nadir pressure on the patient's healthy left side compared to the right side improved with f-PLP. Discussion We discovered two clinical outcomes. First, the f-PLP ensured velopharyngeal closure and an increase in the hypopharyngeal IBP, which potentially improved the UES opening on the healthy side. Second, the f-PLP improved pharyngeal clearance, and the patient felt that it was easier to swallow with the f-PLP. This implies that an f-PLP potentially exhibits a positive effect on swallowing. Conclusions In this case, the f-PLP contributed to improving the pharyngeal passage of a bolus. We suggest that f-PLPs can be used for patients with dysarthria and those with dysphagia with VPI.
- Published
- 2021
31. Appropriate device selection for transcatheter atrial septal defect closure using three-dimensional transesophageal echocardiography
- Author
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Keitaro Shinada, Marjolein C. de Jongh, Hideaki Kanazawa, Mai Kimura, Yuji Itabashi, Akio Kawamura, Hikaru Tsuruta, Jin Endo, Keiichi Fukuda, Mitsushige Murata, Mitsuru Murata, Kotaro Miura, and Hiroki Kitakata
- Subjects
medicine.medical_specialty ,business.industry ,Balloon sizing ,Amplatzer Septal Occluder ,Atrial septal defect closure ,030204 cardiovascular system & hematology ,University hospital ,medicine.disease ,Atrial septum ,03 medical and health sciences ,0302 clinical medicine ,Aneurysm ,Medicine ,Radiology, Nuclear Medicine and imaging ,In patient ,030212 general & internal medicine ,Radiology ,Cardiology and Cardiovascular Medicine ,business ,human activities ,Cardiac imaging - Abstract
Detail morphological evaluation for ASD is essential to achieve successful transcatheter closure. Three-dimensional transesophageal echocardiography (3D-TEE) is emerging, but few studies have comprehensively verified the usefulness of 3D-TEE. We divided 329 patients who underwent transcatheter ASD closure at our university hospital into 157 in the Conventional group evaluated with 2-dimensional transesophageal echocardiography and balloon sizing (BS), and 172 in the 3D-TEE group evaluated with 3D-TEE additionally. We assessed usefulness of 3D-TEE and consider appropriate device selection procedure. Overall, the percentage with re-sizing of device tended to be lower in the 3D-TEE group than in the Conventional group (10.1% vs 6.0%, p = 0.187). Among preprocedural modalities, the device size was mainly decided based on the BS diameter. A logistic regression analysis demonstrated that large atrial septum aneurysms (ASA) were associated with a ≥ 2 mm discrepancy of the BS diameter from the preprocedural 3D-TEE diameter (p
- Published
- 2020
32. Efficacy of treat-and-repair strategy for atrial septal defect with pulmonary arterial hypertension
- Author
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Tsutomu Murakami, Mike Saji, Ichiro Sakamoto, Shinobu Hosokawa, Masao Imai, Koji Nakagawa, Kensuke Matsumoto, Mamoru Nanasato, Yasushi Fuku, Hideaki Kanazawa, Gaku Nakazawa, Yoichi Takaya, Teiji Akagi, Atsushi Yao, Hiroshi Ito, Norio Tada, and Mitsugu Hirokami
- Subjects
medicine.medical_specialty ,Cardiac Catheterization ,Systemic blood ,Hypertension, Pulmonary ,Heart Septal Defects, Atrial ,Internal medicine ,medicine.artery ,Medicine ,Humans ,Familial Primary Pulmonary Hypertension ,Heart Failure ,Pulmonary Arterial Hypertension ,business.industry ,Mortality rate ,medicine.disease ,Flow ratio ,medicine.anatomical_structure ,Treatment Outcome ,Heart failure ,Concomitant ,Pulmonary artery ,Cardiology ,Vascular resistance ,Cardiology and Cardiovascular Medicine ,Complication ,business - Abstract
ObjectiveTherapeutic strategies for atrial septal defect (ASD) with severe pulmonary arterial hypertension (PAH) are controversial. This study aimed to evaluate the efficacy of PAH-specific medications and subsequent transcatheter closure (ie, treat-and-repair strategy) on clinical outcomes.MethodsWe enrolled 42 patients who were referred to 13 institutions for consideration of ASD closure with concomitant PAH and underwent the treat-and-repair strategy. The endpoint was cardiovascular death or hospitalisation due to heart failure or exacerbated PAH.ResultsAt baseline prior to PAH-specific medications, pulmonary to systemic blood flow ratio (Qp:Qs), pulmonary vascular resistance (PVR), and mean pulmonary artery pressure (PAP) were 1.9±0.8, 6.9±3.2 Wood units and 45±15 mm Hg. Qp:Qs was increased to 2.4±1.2, and PVR and mean PAP were decreased to 4.0±1.5 Wood units and 35±9 mm Hg at the time of transcatheter ASD closure after PAH-specific medications. Transcatheter ASD closure was performed without any complications. During a median follow-up period of 33 months (1–126 months) after transcatheter ASD closure, one older patient died and one patient was hospitalised due to heart failure, but the other patients survived with an improvement in WHO functional class. PAP was further decreased after transcatheter ASD closure.ConclusionsThe treat-and-repair strategy results in low complication and mortality rates with a reduction in PAP in selected patients with ASD complicated with PAH who have a favourable response of medical therapy.
- Published
- 2021
33. Tryptophan Metabolism Regulates Proliferative Capacity of Human Pluripotent Stem Cells
- Author
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Sho Tanosaki, Yusuke Soma, Shugo Tohyama, Moon Il Kang, Yuika Morita, Eiji Kobayashi, Kazunori Sasaki, Hidenori Tani, Kotaro Kameda, Otoya Sekine, Keiichi Fukuda, Marina Okada, Yoshikazu Kishino, Hideaki Kanazawa, Kazuaki Nakajima, Taijun Moriwaki, Shota Someya, Jun Fujita, and Tomohiko Umei
- Subjects
0301 basic medicine ,Multidisciplinary ,Metabolite ,02 engineering and technology ,Cell Biology ,Biology ,021001 nanoscience & nanotechnology ,Stem Cell Research ,Regenerative medicine ,Article ,Cell biology ,03 medical and health sciences ,chemistry.chemical_compound ,030104 developmental biology ,Metabolomics ,chemistry ,Cell culture ,Extracellular ,Metabolome ,lcsh:Q ,0210 nano-technology ,Induced pluripotent stem cell ,lcsh:Science ,Kynurenine - Abstract
Summary Human pluripotent stem cells (hPSCs) have a unique metabolic signature for maintenance of pluripotency, self-renewal, and survival. Although hPSCs could be potentially used in regenerative medicine, the prohibitive cost associated with large-scale cell culture presents a major barrier to the clinical application of hPSC. Moreover, without a fully characterized metabolic signature, hPSC culture conditions are not optimized. Here, we performed detailed amino acid profiling and found that tryptophan (TRP) plays a key role in the proliferation with maintenance of pluripotency. In addition, metabolome analyses revealed that intra- and extracellular kynurenine (KYN) is decreased under TRP-supplemented conditions, whereas N-formylkynurenine (NFK), the upstream metabolite of KYN, is increased thereby contributing to proliferation promotion. Taken together, we demonstrate that TRP is indispensable for survival and proliferation of hPSCs. A deeper understanding of TRP metabolism will enable cost-effective large-scale production of hPSCs, leading to advances in regenerative medicine., Graphical Abstract, Highlights • TRP is the only AA that enables enhanced hPSC proliferation by supplementation • hPSCs proliferate with pluripotency after long-term culture in TRP supplementation • The proliferative properties of hPSCs are independent of AhR signaling • TRP-derived NFK contributes to enhanced hPSC proliferation, Cell Biology; Metabolomics; Stem Cell Research
- Published
- 2021
34. Predictors of New-Onset Atrial Tachyarrhythmias After Transcatheter Atrial Septal Defect Closure in Adults
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Atsushi Anzai, Keiichi Fukuda, Kotaro Miura, Yuji Itabashi, Jin Endo, Takashi Kawakami, Hikaru Tsuruta, Hideaki Kanazawa, Shinsuke Yuasa, Kentaro Hayashida, Akio Kawamura, Takahide Arai, and Mai Kimura
- Subjects
Pulmonary and Respiratory Medicine ,Adult ,medicine.medical_specialty ,Cardiac Catheterization ,Adolescent ,medicine.medical_treatment ,Left atrium ,Patient characteristics ,Catheter ablation ,030204 cardiovascular system & hematology ,Heart Septal Defects, Atrial ,New onset ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Tachycardia ,medicine ,Humans ,In patient ,030212 general & internal medicine ,Heart Atria ,Stroke ,business.industry ,Atrial septal defect closure ,medicine.disease ,Brain natriuretic peptide ,medicine.anatomical_structure ,Treatment Outcome ,Cardiology ,Cardiology and Cardiovascular Medicine ,business - Abstract
New-onset atrial tachyarrhythmia (ATA) often develops after atrial septal defect (ASD) closure. Its development raises some potential concerns such as stroke and bleeding complications caused by anticoagulant therapy and limited access to the left atrium for catheter ablation. Although it is essential to identify the risk factors of new-onset ATA, few studies have examined these factors. This study investigated unknown risk factors for the development of new-onset ATA after transcatheter ASD closure in patients without a history of ATA.A total of 238 patients without a history of ATA, aged ≥18 years and who underwent transcatheter ASD closure at the current hospital were reviewed. Patient characteristics were compared between the groups with and without new-onset ATA. The factors associated with new-onset ATA were examined using univariate and multivariable analyses.Thirteen (13) (5.5%) patients experienced ATA during follow-up (mean, 21±14 months). Compared with patients without new-onset ATA, patients with new-onset ATA were older (48±18 vs 66±11 years; p0.001) and had high brain natriuretic peptide (BNP) levels (36±36 vs 177±306 pg/mL; p0.001). On multivariable analysis, BNP ≥40 pg/mL before ASD closure was associated with new-onset ATA after adjusting for age (OR, 4.91; 95% CI, 1.22-19.8; p=0.025).Patients with BNP levels40 pg/mL before transcatheter ASD closure may have a higher risk of developing new-onset ATA.
- Published
- 2020
35. CURRENT STATUS AND CATHETER CLOSURE OF IATROGENIC ATRIAL SEPTAL DEFECT CAUSED BY MITRACLIP PROCEDURE
- Author
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Teiji Akagi, Yoichi Takaya, Takashi Miki, Hidehiko Hara, and Hideaki Kanazawa
- Subjects
Cardiology and Cardiovascular Medicine - Published
- 2022
36. A dilemma regarding the treatment of emergency percutaneous coronary intervention patients with prior contrast reaction: What can we do to prevent 'one lethal reaction'?
- Author
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Hideaki Kanazawa
- Subjects
business.industry ,Premedication ,medicine.medical_treatment ,media_common.quotation_subject ,Contrast Media ,Percutaneous coronary intervention ,Prognosis ,Dilemma ,Percutaneous Coronary Intervention ,Anesthesia ,medicine ,Humans ,Contrast (vision) ,Cardiology and Cardiovascular Medicine ,business ,Emergency percutaneous coronary intervention ,media_common - Published
- 2021
37. Appropriate device selection for transcatheter atrial septal defect closure using three-dimensional transesophageal echocardiography
- Author
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Hiroki, Kitakata, Yuji, Itabashi, Hideaki, Kanazawa, Kotaro, Miura, Mai, Kimura, Keitaro, Shinada, Marjolein C, de Jongh, Jin, Endo, Hikaru, Tsuruta, Mitsushige, Murata, Akio, Kawamura, Mitsuru, Murata, and Keiichi, Fukuda
- Subjects
Adult ,Aged, 80 and over ,Male ,Cardiac Catheterization ,Adolescent ,Septal Occluder Device ,Clinical Decision-Making ,Echocardiography, Three-Dimensional ,Middle Aged ,Prosthesis Design ,Heart Septal Defects, Atrial ,Young Adult ,Treatment Outcome ,Predictive Value of Tests ,Humans ,Female ,Child ,Echocardiography, Transesophageal ,Aged ,Retrospective Studies - Abstract
Detail morphological evaluation for ASD is essential to achieve successful transcatheter closure. Three-dimensional transesophageal echocardiography (3D-TEE) is emerging, but few studies have comprehensively verified the usefulness of 3D-TEE. We divided 329 patients who underwent transcatheter ASD closure at our university hospital into 157 in the Conventional group evaluated with 2-dimensional transesophageal echocardiography and balloon sizing (BS), and 172 in the 3D-TEE group evaluated with 3D-TEE additionally. We assessed usefulness of 3D-TEE and consider appropriate device selection procedure. Overall, the percentage with re-sizing of device tended to be lower in the 3D-TEE group than in the Conventional group (10.1% vs 6.0%, p = 0.187). Among preprocedural modalities, the device size was mainly decided based on the BS diameter. A logistic regression analysis demonstrated that large atrial septum aneurysms (ASA) were associated with a ≥ 2 mm discrepancy of the BS diameter from the preprocedural 3D-TEE diameter (p 0.05). Compared to the Amplatzer Septal Occluder, the differences in device size and the preprocedural ASD measurement were greater when using the Occlutech Figulla Flex II Occluder (FFII). Particularly, among the patients implanted with FFIIs, the discrepancies of the device size from the 3D-TEE measurement were greater in patients with large ASA than those with small ASA. Preprocedural 3D-TEE is useful to select the appropriate device size. Particularly, it is necessary to select a much larger device than that derived from the preprocedural 3D-TEE measurement when using FFII in patients with a septal aneurysm.
- Published
- 2020
38. A Case of Post-trauma Dysphagia: Peculiar Swallowing Dynamics Due to Associated Laryngeal Paralysis
- Author
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Kenjiro Kunieda, Takafumi Sugi, Hirotatsu Takahashi, Ichiro Fujishima, Hiroshi Yaguchi, Masahiro Sugiyama, Hideaki Kanazawa, and Ayano Takinami
- Subjects
medicine.medical_specialty ,Rehabilitation ,dysphagia ,business.industry ,upper esophageal sphincter opening ,medicine.medical_treatment ,digestive, oral, and skin physiology ,Nerve Paralysis ,Case Report ,General Medicine ,Aspiration pneumonia ,medicine.disease ,Dysphagia ,Surgery ,Head trauma ,Swallowing ,Laryngeal paralysis ,Percutaneous endoscopic gastrostomy ,head trauma ,medicine ,medicine.symptom ,business ,bilateral associated laryngeal paralysis - Abstract
Background: Associated laryngeal paralysis (ALP) is defined as vagus nerve impairment combined with other lower cranial nerve paralysis. Traumatic ALP is reported infrequently. Case: A 72-year-old man was injured on the back of the head when a large tree fell on him; he was admitted to a general hospital, where he was diagnosed with brain concussion and Guillain-Barre syndrome (GBS). The patient developed aspiration pneumonia due to severe dysphagia. Although he underwent treatment and rehabilitation for 6 months, some disabilities persisted, and a percutaneous endoscopic gastrostomy tube was placed. Six months after the accident, the patient was transferred to our rehabilitation hospital. Videoendoscopic examination and videofluoroscopy revealed persistent upper esophageal sphincter (UES) opening, left dominant bilateral IX and X nerve paralysis, and left XII nerve paralysis; moreover, these examinations showed that the swallowing reflex was absent, although a bolus could pass through the UES. We suspected that the patient’s condition was not GBS and performed head computed tomography and magnetic resonance imaging; these revealed a bone fracture at the skull base. Consequently, the patient’s diagnosis was changed to bilateral ALP. He received swallowing rehabilitation for 2 months and could orally consume alternative nutrition. Finally, the patient was able to eat orally texture-modified foods (Food Intake LEVEL Scale level 8). Discussion: While post-trauma dysphagia due to bilateral ALP might be severe, patients can regain the ability to eat orally if clinicians understand the etiology of dysphagia and provide appropriate swallowing rehabilitation techniques, including patient position adjustment while eating and selection of food textures.
- Published
- 2020
39. Zero-Contrast Transcatheter Closure of Patent Ductus Arteriosus Guided by Multiple Imaging Modalities
- Author
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Takashi Kawakami, Hideaki Kanazawa, Mai Kimura, Kentaro Hayashida, Takahide Arai, Keiichi Fukuda, Kotaro Miura, and Shinsuke Yuasa
- Subjects
Adult ,Male ,medicine.medical_specialty ,Cardiac Catheterization ,business.industry ,Closure (topology) ,Contraindications, Drug ,Contrast Media ,Contrast (music) ,Kidney Transplantation ,Multimodal Imaging ,Imaging modalities ,Cardiac Imaging Techniques ,medicine.anatomical_structure ,Surgery, Computer-Assisted ,Ductus arteriosus ,medicine ,Humans ,Radiology ,Renal Insufficiency ,Cardiology and Cardiovascular Medicine ,business ,Ductus Arteriosus, Patent ,Echocardiography, Transesophageal ,Ultrasonography, Interventional - Published
- 2019
40. Efficient Large-Scale 2D Culture System for Human Induced Pluripotent Stem Cells and Differentiated Cardiomyocytes
- Author
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Marina Okada, Kazuaki Nakajima, Sayaka Kanaami, Shugo Tohyama, Kazuho Sakamoto, Sho Tanosaki, Shota Someya, Jun Fujita, Masami Kodama, Akinori Hirano, Tomohisa Seki, Rei Ohno, Shinji Kawaguchi, Keiichi Fukuda, Junko Kurokawa, Yoshikazu Kishino, Hideaki Kanazawa, Miho Yamaguchi, Eiji Kobayashi, and Chihana Fujita
- Subjects
0301 basic medicine ,Culture plates ,purification ,Cardiac differentiation ,Induced Pluripotent Stem Cells ,Primary Cell Culture ,iPSCs ,regenerative medicine ,cardiomyocytes ,Biology ,Biochemistry ,03 medical and health sciences ,Report ,2D culture ,Genetics ,Humans ,Myocytes, Cardiac ,Human Induced Pluripotent Stem Cells ,lcsh:QH301-705.5 ,Cells, Cultured ,Cell Proliferation ,lcsh:R5-920 ,Cell Differentiation ,Cell Biology ,Cell biology ,Culture Media ,030104 developmental biology ,lcsh:Biology (General) ,large scale ,lcsh:Medicine (General) ,Developmental Biology - Abstract
Summary Cardiac regenerative therapies utilizing human induced pluripotent stem cells (hiPSCs) are hampered by ineffective large-scale culture. hiPSCs were cultured in multilayer culture plates (CPs) with active gas ventilation (AGV), resulting in stable proliferation and pluripotency. Seeding of 1 × 106 hiPSCs per layer yielded 7.2 × 108 hiPSCs in 4-layer CPs and 1.7 × 109 hiPSCs in 10-layer CPs with pluripotency. hiPSCs were sequentially differentiated into cardiomyocytes (CMs) in a two-dimensional (2D) differentiation protocol. The efficiency of cardiac differentiation using 10-layer CPs with AGV was 66%–87%. Approximately 6.2–7.0 × 108 cells (4-layer) and 1.5–2.8 × 109 cells (10-layer) were obtained with AGV. After metabolic purification with glucose- and glutamine-depleted and lactate-supplemented media, a massive amount of purified CMs was prepared. Here, we present a scalable 2D culture system using multilayer CPs with AGV for hiPSC-derived CMs, which will facilitate clinical applications for severe heart failure in the near future., Graphical Abstract, Highlights • Efficient mass production of hiPSCs by multilayer culture plates with AGV • Efficient mass production of hiPSC-CMs using a massive 2D culture system with AGV • Mass production of pure hiPSC-CMs via metabolic selection, In this article, Fujita and colleagues show that human induced pluripotent stem cells (hiPSCs) and hiPSC-derived cardiomyocytes (hiPSC-CMs) are stably and efficiently produced using multilayer culture plates with an active gas ventilation system because of stable CO2 and O2 concentration in culture media. Large numbers of obtained hiPSC-CMs are metabolically purified under glucose- and glutamine-depleted and lactate-supplemented conditions.
- Published
- 2017
41. Efficacy of treat-and-repair strategy for atrial septal defect with pulmonary arterial hypertension.
- Author
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Yoichi Takaya, Teiji Akagi, Ichiro Sakamoto, Hideaki Kanazawa, Gaku Nakazawa, Tsutomu Murakami, Atsushi Yao, Mamoru Nanasato, Mike Saji, Mitsugu Hirokami, Yasushi Fuku, Shinobu Hosokawa, Norio Tada, Kensuke Matsumoto, Masao Imai, Koji Nakagawa, Hiroshi Ito, Takaya, Yoichi, Akagi, Teiji, and Sakamoto, Ichiro
- Subjects
ATRIAL septal defects ,PULMONARY arterial hypertension ,OLDER patients ,HEART failure ,VASCULAR resistance - Abstract
Objective: Therapeutic strategies for atrial septal defect (ASD) with severe pulmonary arterial hypertension (PAH) are controversial. This study aimed to evaluate the efficacy of PAH-specific medications and subsequent transcatheter closure (ie, treat-and-repair strategy) on clinical outcomes.Methods: We enrolled 42 patients who were referred to 13 institutions for consideration of ASD closure with concomitant PAH and underwent the treat-and-repair strategy. The endpoint was cardiovascular death or hospitalisation due to heart failure or exacerbated PAH.Results: At baseline prior to PAH-specific medications, pulmonary to systemic blood flow ratio (Qp:Qs), pulmonary vascular resistance (PVR), and mean pulmonary artery pressure (PAP) were 1.9±0.8, 6.9±3.2 Wood units and 45±15 mm Hg. Qp:Qs was increased to 2.4±1.2, and PVR and mean PAP were decreased to 4.0±1.5 Wood units and 35±9 mm Hg at the time of transcatheter ASD closure after PAH-specific medications. Transcatheter ASD closure was performed without any complications. During a median follow-up period of 33 months (1-126 months) after transcatheter ASD closure, one older patient died and one patient was hospitalised due to heart failure, but the other patients survived with an improvement in WHO functional class. PAP was further decreased after transcatheter ASD closure.Conclusions: The treat-and-repair strategy results in low complication and mortality rates with a reduction in PAP in selected patients with ASD complicated with PAH who have a favourable response of medical therapy. [ABSTRACT FROM AUTHOR]- Published
- 2022
- Full Text
- View/download PDF
42. A rare case of unroofed coronary sinus with a secundum atrial septal defect incidentally detected by computed tomography
- Author
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Masahiro Jinzaki, Yoshitake Yamada, Keiichi Fukuda, Satoshi Shoji, and Hideaki Kanazawa
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medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,Rare case ,Septum secundum ,Medicine ,Radiology, Nuclear Medicine and imaging ,Computed tomography ,Radiology ,Cardiology and Cardiovascular Medicine ,business ,Unroofed coronary sinus - Published
- 2020
43. Nocturnal intermittent hypoxia and short sleep duration are independently associated with elevated C-reactive protein levels in patients with coronary artery disease
- Author
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Ryo Yanagisawa, Ryoma Fukuoka, Takashi Kawakami, Shinsuke Yuasa, Takashi Kohno, Keiichi Fukuda, Shun Kohsaka, Motoaki Sano, Kentaro Hayashida, Hideaki Kanazawa, and Yuichiro Maekawa
- Subjects
Male ,medicine.medical_specialty ,Time Factors ,medicine.medical_treatment ,Coronary Artery Disease ,030204 cardiovascular system & hematology ,Coronary artery disease ,03 medical and health sciences ,Sleep Apnea Syndromes ,0302 clinical medicine ,Risk Factors ,Internal medicine ,medicine ,Humans ,Oximetry ,cardiovascular diseases ,Hypoxia ,Aged ,medicine.diagnostic_test ,business.industry ,Percutaneous coronary intervention ,Intermittent hypoxia ,General Medicine ,medicine.disease ,Sleep in non-human animals ,Pathophysiology ,Confidence interval ,Pulse oximetry ,C-Reactive Protein ,Endocrinology ,Cardiology ,Breathing ,Female ,Sleep ,business ,030217 neurology & neurosurgery - Abstract
Sleep-disordered breathing (SDB) or short sleep duration and coronary artery disease (CAD) are related, yet, the prevalence of SDB and short sleep duration as well as their mechanism remain unknown. Enhanced vascular inflammation is also implicated as one of the pathophysiologic mechanisms in CAD. The aims of this study were to evaluate the prevalence of patients with SDB and short sleep duration, and to examine their relationship with serum C-reactive protein (CRP) level in CAD patients.We evaluated 161 CAD patients who underwent percutaneous coronary intervention, using nocturnal pulse oximetry, a non-invasive screening method for nocturnal intermittent hypoxia. Based on three percent oxygen desaturation index (3% ODI), the patients were divided into nocturnal intermittent hypoxia (3% ODI ≥ 15; n = 45) and control groups (3% ODI 15, n = 116). The nocturnal intermittent hypoxia group had higher body mass index and serum CRP level compared with the control group. Short sleep duration (6 h, n = 45) was also associated with increased CRP level compared with the control group (≥6 h, n = 116). In multiple regression analysis, nocturnal intermittent hypoxia (β = 0.332, 95% confidence interval [CI] 0.102-0.562, P = 0.005) and short sleep duration (β = 0.311, 95% CI 0.097-0.526, P = 0.005) were both independent determinants for log serum CRP level.Nocturnal intermittent hypoxia and short sleep duration were independently associated with elevated serum CRP level in CAD patients, suggesting that both SDB and sleep shortage are associated with enhanced inflammation in CAD patients. SDB and sleep duration may be important modifiable factors in the clinical management of patients with CAD.
- Published
- 2017
44. Evaluation of a palatal lift prosthesis with a flexible lift in a lower cranial nerve palsy patient with dysphagia using high-resolution manometry: A case report.
- Author
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Akiko Nomoto, Tomohisa Ohno, Kenjiro Kunieda, Hideaki Kanazawa, Takashi Shigematsu, Kyoko Hojo, Akio Shimizu, Shunsuke Minakuchi, and Ichiro Fujishima
- Subjects
CRANIAL nerves ,VELOPHARYNGEAL insufficiency ,ESOPHAGEAL motility disorders ,PROSTHETICS ,DEGLUTITION disorders ,ESOPHAGOGASTRIC junction ,PARALYSIS - Abstract
Patient: Palatal lift prostheses (PLPs) are used for dysarthria caused by velopharyngeal incompetence (VPI) and improving hypernasal speech. In this case, we used a PLP with a flexible lift (f-PLP) in a patient with dysphagia associated with VPI due to right-sided cranial nerve injuries after a skull base surgery. We examined its efficacy in swallowing biomechanics and swallowing function using high-resolution manometry (HRM) and videofluoroscopic examination of swallowing (VF). The patient felt that it was easier to swallow with f-PLP. Furthermore, VF indicated that the pharyngeal residue with f-PLP was less than without it. HRM showed that velopharyngeal pressure and intrabolus pressure (IBP) with f-PLP were higher than those without it. Additionally, the upper esophageal sphincter (UES) relaxation time and UES nadir pressure on the patient's healthy left side compared to the right side improved with f-PLP.Discussion: We discovered two clinical outcomes. First, the f-PLP ensured velopharyngeal closure and an increase in the hypopharyngeal IBP, which potentially improved the UES opening on the healthy side. Second, the f-PLP improved pharyngeal clearance, and the patient felt that it was easier to swallow with the f-PLP. This implies that an f-PLP potentially exhibits a positive effect on swallowing.Conclusions: In this case, the f-PLP contributed to improving the pharyngeal passage of a bolus. We suggest that f-PLPs can be used for patients with dysarthria and those with dysphagia with VPI. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
45. Staged transcatheter closure for atrial septal defect and patent ductus arteriosus: a case report
- Author
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Yasuyuki Shiraishi, Keiichi Fukuda, Yusuke Soma, and Hideaki Kanazawa
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congenital, hereditary, and neonatal diseases and abnormalities ,medicine.medical_specialty ,business.industry ,Patent ductus arteriosus ,Hemodynamics ,Case Reports ,medicine.disease ,Haemolysis ,Shunt (medical) ,Surgery ,medicine.anatomical_structure ,Ductus arteriosus ,Case report ,Atrial septal defect ,medicine ,Cardiac defects ,cardiovascular diseases ,Thrombus ,Cardiology and Cardiovascular Medicine ,business ,Congenital heart disease ,Therapeutic strategy ,Calcification - Abstract
BackgroundAtrial septal defect (ASD) and patent ductus arteriosus (PDA) are both common congenital heart diseases, but the combination of these two cardiac defects is extremely rare, and the therapeutic strategy is controversial.Case summaryWe treated an adult patient with combined ASD and PDA, and safely attained a successful outcome with two-stage transcatheter closure, which is PDA closure preceding ASD closure, to prevent serious complications.DiscussionTranscatheter closure of one of the defects is now widely accepted as an alternative to surgical closure. In addition, adults with both ASD and PDA are better suited for transcatheter closure than surgical closure. One of the reasons is the difficulty to ligate the ductus arteriosus of an adult patient due to its friability and calcification. Meanwhile, simultaneous combined transcatheter closure of ASD and PDA can result in serious complications, such as thrombocytopenia and haemolysis, whose mechanism is considered to be the destruction of platelets and red blood cells by the residual shunt through implanted devices. Additionally, antiplatelet therapy that prevents device-related thrombus formation after ASD closure can possibly exacerbate thrombocytopenia and haemolysis. Therefore, the staged strategy is reasonable from the perspectives of antiplatelet therapy and haemodynamic changes.
- Published
- 2019
46. Selective elimination of undifferentiated human pluripotent stem cells using pluripotent state-specific immunogenic antigen Glypican-3
- Author
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Kazuya Ofuji, Keiichi Fukuda, Sho Tanosaki, Marina Okada, Yoshikazu Kishino, Manami Shimomura, Shota Someya, Jun Fujita, Shugo Tohyama, Kazuaki Nakajima, Tetsuya Nakatsura, Yoshitaka Tada, Toshihiro Suzuki, Hideaki Kanazawa, Satoru Senju, and Tomohisa Seki
- Subjects
0301 basic medicine ,Models, Molecular ,medicine.medical_treatment ,Induced Pluripotent Stem Cells ,Biophysics ,Human leukocyte antigen ,Mice, SCID ,Biology ,Biochemistry ,Glypican 3 ,Regenerative medicine ,Cell Line ,03 medical and health sciences ,0302 clinical medicine ,Antigen ,Glypicans ,Mice, Inbred NOD ,Neoplasms ,HLA-A2 Antigen ,medicine ,Cytotoxic T cell ,Animals ,Humans ,Induced pluripotent stem cell ,Molecular Biology ,Immunogenicity ,Cell Differentiation ,Cell Biology ,Immunotherapy ,030104 developmental biology ,030220 oncology & carcinogenesis ,Cancer research ,T-Lymphocytes, Cytotoxic - Abstract
Immunogenicity of immature pluripotent stem cells is a topic of intense debate. Immunogenic antigens, which are specific in pluripotent states, have not been described previously. In this study, we identified glypican-3 (GPC3), a known carcinoembryonic antigen, as a pluripotent state-specific immunogenic antigen. Additionally, we validated the applicability of human leukocyte antigen (HLA)-class I-restricted GPC3-reactive cytotoxic T lymphocytes (CTLs) in the removal of undifferentiated pluripotent stem cells (PSCs) from human induced pluripotent stem cell (hiPSC)-derivatives. HiPSCs uniquely express GPC3 in pluripotent states and were rejected by GPC3-reactive CTLs, which were sensitized with HLA-class I-restricted GPC3 peptides. Furthermore, GPC3-reactive CTLs selectively removed undifferentiated PSCs from hiPSC-derivatives in vitro and inhibited tumor formation in vivo. Our results demonstrate that GPC3 works as a pluripotent state-specific immunogenic antigen in hiPSCs and is applicable to regenerative medicine as a method of removing undifferentiated PSCs, which are the main cause of tumor formation.
- Published
- 2019
47. Molecular and cellular neurocardiology: development, and cellular and molecular adaptations to heart disease
- Author
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Keiichi Fukuda, Donald B. Hoover, Susan J. Birren, Beth A. Habecker, Mark E. Anderson, Hideaki Kanazawa, Neil Herring, David J. Paterson, and Crystal M. Ripplinger
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0301 basic medicine ,Nervous system ,Physiological function ,Heart disease ,Physiology ,Extramural ,Disease ,Biology ,medicine.disease ,Neurocardiology ,Cardiovascular physiology ,03 medical and health sciences ,030104 developmental biology ,medicine.anatomical_structure ,Heart innervation ,medicine ,Neuroscience - Abstract
The nervous system and cardiovascular system develop in concert and are functionally interconnected in both health and disease. This white paper focuses on the cellular and molecular mechanisms that underlie neural-cardiac interactions during development, during normal physiological function in the mature system, and during pathological remodelling in cardiovascular disease. The content on each subject was contributed by experts, and we hope that this will provide a useful resource for newcomers to neurocardiology as well as aficionados.
- Published
- 2016
48. Glutamine Oxidation Is Indispensable for Survival of Human Pluripotent Stem Cells
- Author
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Jun Fujita, Yoji Sato, Shugo Tohyama, Yoshikazu Kishino, Rei Ohno, Satoshi Yasuda, Keiichi Fukuda, Tomohisa Seki, Takako Hishiki, Marina Okada, Fumiyuki Hattori, Makoto Suematsu, Motoaki Sano, Akinori Hirano, Hideaki Kanazawa, Kazuaki Nakajima, Takuya Kuroda, Shinsuke Yuasa, and Tomomi Matsuura
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Pluripotent Stem Cells ,0301 basic medicine ,Cell Survival ,Physiology ,Glutamine ,Citric Acid Cycle ,Mitochondrion ,Biology ,Cell Line ,03 medical and health sciences ,Adenosine Triphosphate ,Pyruvic Acid ,Humans ,Glycolysis ,Induced pluripotent stem cell ,Molecular Biology ,ACO2 ,Cell Biology ,Citric acid cycle ,Glucose ,030104 developmental biology ,Biochemistry ,Anaerobic glycolysis ,Energy source ,Oxidation-Reduction - Abstract
Human pluripotent stem cells (hPSCs) are uniquely dependent on aerobic glycolysis to generate ATP. However, the importance of oxidative phosphorylation (OXPHOS) has not been elucidated. Detailed amino acid profiling has revealed that glutamine is indispensable for the survival of hPSCs. Under glucose- and glutamine-depleted conditions, hPSCs quickly died due to the loss of ATP. Metabolome analyses showed that hPSCs oxidized pyruvate poorly and that glutamine was the main energy source for OXPHOS. hPSCs were unable to utilize pyruvate-derived citrate due to negligible expression of aconitase 2 (ACO2) and isocitrate dehydrogenase 2/3 (IDH2/3) and high expression of ATP-citrate lyase. Cardiomyocytes with mature mitochondria were not able to survive without glucose and glutamine, although they were able to use lactate to synthesize pyruvate and glutamate. This distinguishing feature of hPSC metabolism allows preparation of clinical-grade cell sources free of undifferentiated hPSCs, which prevents tumor formation during stem cell therapy.
- Published
- 2016
49. A 'bowing' pedunculated large thrombus in the left ventricle and its formation
- Author
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Hideaki Kanazawa, Yohei Numasawa, Takashi Kawakami, Kazuhiko Shimizu, Yoshihiko Mochizuki, Ichiro Kashima, and Keiichi Fukuda
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medicine.medical_specialty ,medicine.anatomical_structure ,Ventricle ,business.industry ,Internal medicine ,medicine ,Cardiology ,Thrombus ,Left ventricular thrombus ,Cardiology and Cardiovascular Medicine ,medicine.disease ,business - Published
- 2016
50. A Novel Mechanism of Atrioventricular Block Following Transcatheter Closure of an Atrial Septal Defect
- Author
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Motoaki Sano, Takahiko Nishiyama, Hideaki Kanazawa, Sho Tanosaki, Mitsushige Murata, Mai Kimura, Yuji Itabashi, Keiichi Fukuda, Takashi Kohno, Seiji Takatsuki, Osamu Igawa, Akira Kunitomi, Hikaru Tsuruta, Yoshiyasu Aizawa, Tsunehisa Yamamoto, Yuichiro Maekawa, and Shinichi Goto
- Subjects
Cardiac Catheterization ,congenital, hereditary, and neonatal diseases and abnormalities ,medicine.medical_specialty ,Septal Occluder Device ,business.industry ,Amplatzer Septal Occluder ,Middle Aged ,030204 cardiovascular system & hematology ,medicine.disease ,Heart Septal Defects, Atrial ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,cardiovascular system ,Cardiology ,Humans ,Medicine ,Female ,cardiovascular diseases ,030212 general & internal medicine ,Atrioventricular Block ,Cardiology and Cardiovascular Medicine ,business ,Atrioventricular block ,After treatment - Abstract
A 58-year-old woman visited the emergency room for faintness on exertion 1 month after treatment of an atrial septal defect (ASD) by transcatheter closure (Amplatzer septal occluder [ASO], St. Jude Medical, St. Paul, Minnesota). An electrocardiogram showed advanced atrioventricular (AV) block ([
- Published
- 2016
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