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Cardiovascular disease remains a global health concern. Stem cell therapy utilizing human cardiac progenitor cells (hCPCs) shows promise in treating cardiac vascular disease. However, limited availability and senescence of hCPCs hinder their widespread use. To address these challenges, researchers are exploring innovative approaches. In this study, a bioengineered cell culture plate was developed to mimic the natural cardiac tissue microenvironment. It was coated with a combination of extracellular matrix (ECM) peptide motifs and mussel adhesive protein (MAP). The selected ECM peptide motifs, derived from fibronectin and vitronectin, play crucial roles in hCPCs. Results revealed that the Fibro-P and Vitro-P coated plates significantly improved hCPC adhesion, proliferation, migration, and differentiation compared to uncoated plates. Additionally, long-term culture on the coated plates delayed cellular senescence and maintained hCPC stemness. These enhancements were attributed to the activation of integrin downstream signaling pathways. The findings suggest that the engineered ECM peptide motif-MAP-coated plates hold potential for enhancing the therapeutic efficacy of stem cell-based therapies in cardiac tissue engineering and regenerative medicine., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Sang-Mo Kwon reports financial support was provided by Korean Fund for Regenerative Medicine. Sang-Mo Kwon reports financial support was provided by National Research Foundation., (Copyright © 2024. Published by Elsevier B.V.)

Stem cell-based therapies with clinical applications require millions of cells. Therefore, repeated subculture is essential for cellular expansion, which is often complicated by replicative senescence. Cellular senescence contributes to reduced stem cell regenerative potential as it inhibits stem cell proliferation and differentiation as well as the activation of the senescence-associated secretory phenotype (SASP). In this study, we employed MHY-1685, a novel mammalian target of rapamycin (mTOR) inhibitor, and examined its long-term priming effect on the activities of senile human cardiac stem cells (hCSCs) and the functional benefits of primed hCSCs after transplantation. In vitro experiments showed that the MHY-1685‒primed hCSCs exhibited higher viability in response to oxidative stress and an enhanced proliferation potential compared to that of the unprimed senile hCSCs. Interestingly, priming MHY-1685 enhanced the expression of stemness-related markers in senile hCSCs and provided the differentiation potential of hCSCs into vascular lineages. In vivo experiment with echocardiography showed that transplantation of MHY-1685‒primed hCSCs improved cardiac function than that of the unprimed senile hCSCs at 4 weeks post-MI. In addition, hearts transplanted with MHY-1685-primed hCSCs exhibited significantly lower cardiac fibrosis and higher capillary density than that of the unprimed senile hCSCs. In confocal fluorescence imaging, MHY-1685‒primed hCSCs survived for longer durations than that of the unprimed senile hCSCs and had a higher potential to differentiate into endothelial cells (ECs) within the infarcted hearts. These findings suggest that MHY-1685 can rejuvenate senile hCSCs by modulating autophagy and that as a senescence inhibitor, MHY-1685 can provide opportunities to improve hCSC-based myocardial regeneration., (© 2021. The Author(s).)

Background: Despite promising advances in stem cell-based therapy, the treatment of ischemic cardiovascular diseases remains a big challenge due to both the insufficient in vivo viability of transplanted cells and poor angiogenic potential of stem cells. The goal of this study was to develop therapeutic human cardiac progenitor cells (hCPCs) for ischemic cardiovascular diseases with a novel M13 peptide carrier., Method: In this study, an engineered M13 peptide carrier was successfully generated using a QuikChange Kit. The cellular function of M13 peptide carrier-treated hCPCs was assessed using a tube formation assay and scratch wound healing assay. The in vivo engraftment and cell survival bioactivities of transplanted cells were demonstrated by immunohistochemistry after hCPC transplantation into a myocardial infarction animal model., Results: The engineered M13 RGD+SDKP peptide carrier, which expressed RGD peptide on PIII site and SDKP peptide on PVIII site, did not affect morphologic change and proliferation ability in hCPCs. In contrast, hCPCs treated with M13 RGD+SDKP showed enhanced angiogenic capacity, including tube formation and migration capacity. Moreover, transplanted hCPCs with M13 RGD+SDKP were engrafted into the ischemic region and promoted in vivo cell survival., Conclusion: Our present data provides a promising protocol for CPC-based cell therapy via short-term cell priming of hCPCs with engineered M13 RGD+SDKP before cell transplantation for treatment of cardiovascular disease.

Cardiac progenitor cells (CPCs) are resident stem cells present in a small portion of ischemic hearts and function in repairing the damaged heart tissue. Intense oxidative stress impairs cell metabolism thereby decreasing cell viability. Protecting CPCs from undergoing cellular apoptosis during oxidative stress is crucial in optimizing CPC-based therapy. Histochrome (sodium salt of echinochrome A-a common sea urchin pigment) is an antioxidant drug that has been clinically used as a pharmacologic agent for ischemia/reperfusion injury in Russia. However, the mechanistic effect of histochrome on CPCs has never been reported. We investigated the protective effect of histochrome pretreatment on human CPCs (hCPCs) against hydrogen peroxide (H 2 O 2 )-induced oxidative stress. Annexin V/7-aminoactinomycin D (7-AAD) assay revealed that histochrome-treated CPCs showed significant protective effects against H 2 O 2 -induced cell death. The anti-apoptotic proteins B-cell lymphoma 2 (Bcl-2) and Bcl-xL were significantly upregulated, whereas the pro-apoptotic proteins BCL2-associated X (Bax), H 2 O 2 -induced cleaved caspase-3, and the DNA damage marker, phosphorylated histone (γH2A.X) foci, were significantly downregulated upon histochrome treatment of hCPCs in vitro. Further, prolonged incubation with histochrome alleviated the replicative cellular senescence of hCPCs. In conclusion, we report the protective effect of histochrome against oxidative stress and present the use of a potent and bio-safe cell priming agent as a potential therapeutic strategy in patient-derived hCPCs to treat heart disease.

Stem cell technology holds immense potential for revolutionizing medicine, particularly in regenerative treatment for heart disease. The unique capacity of stem cells to differentiate into diverse cell types offers promise in repairing damaged tissues and implanting organs. Ensuring the quality of differentiated cells, essential for specific functions, demands in-depth analysis. However, this process consumes time and incurs substantial costs while invasive methods may alter stem cell features during differentiation and deplete cell numbers. To address these challenges, we propose a non-invasive strategy, using cellular respiration, to assess the quality of differentiation-induced stem cells, notably cardiovascular stem cells. This evaluation employs an electronic nose (E-Nose) and neural pattern separation (NPS). Our goal is to assess differentiation-induced cardiac stem cells (DICs) quality through E-Nose data analysis and compare it with standard commercial human cells (SCHCs). Sensitivity and specificity were evaluated by interacting SCHCs and DICs with the E-Nose, achieving over 90% classification accuracy. Employing selective combinations optimized by NPS, E-Nose successfully classified all six cell types. Consequently, the relative similarity among DICs like cardiomyocytes, endothelial cells with SCHCs was established relied on comparing response data from the E-Nose sensor without resorting to complex evaluations. [ABSTRACT FROM AUTHOR]