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Purpose: This study evaluated the clinical results of zoledronic acid in the treatment of early osteonecrosis of the femoral head (ONFH). Materials and Methods: Study retrospectively analyzed 60 patients with zoledronic acid with bone marrow stem cell (BMSC) implantation (The study group) and 64 patients with BMSC implantation (The control group). The primary evaluation index included VAS, HHS, collapsed rate, and total hip replacement arthroplasty (THA) conversion rate. Results: The study group had a lower VAS (1.12 ± 0.22 vs 1.44 ± 0.32) and higher HHS (75.07 ± 3.66 vs 68.78 ± 2.24) compared to the control group in 6 months after surgery (P < 0.05). In the study group, 12 hips (20%) collapsed, and 7 of 60 hips (11.67%) required THA surgery at the last follow-up. However, 25 hips (38.8%) collapsed in the control group, and 19 hips (29.69%) required THA surgery. The study group had a lower collapsed rate (P = 0.029) and THA conversion rate (P = 0.016) in survival analysis. Conclusion: Zoledronic acid and BMSC implantation in the treatment of early ONFH is safe and effective, reduces pain shortens recovery time, and reduces collapsed rate and THA conversion rate in ONFH patients. [ABSTRACT FROM AUTHOR]

OBJECTIVE: In this study, we aimed to investigate the role of bone marrow-derived mesenchymal stem cells (BMSC) on the molecular mechanisms involved in the removal of endometrial adhesions and the implantation process in the experimentally-created Asherman syndrome model in rats. MATERIALS AND METHODS: An experimental model chemical agent was used. Culture medium (CM), only BMSC, 48-hour culture medium (Niche), and BMSC+ niche were used as therapy. Each group was divided into two subgroups, and changes in the endometrial tissue were investigated by histochemical and immunohistochemical staining. RESULTS: The results of the study show that BMSCs exhibit therapeutic properties in endometrial damage, increase endometrial thickness and vascularization, and contribute to the implantation of embryos by reducing fibrous areas. These results are promising for the prevention of Asherman-induced infertility. CONCLUSIONS: It has been shown that BMSC and Niche applications can be helpful in preventing adhesion molecules in the mechanisms that cause infertility. [ABSTRACT FROM AUTHOR]

Objective(s): Remote organ injury is a phenomenon that could happen following myocardial infarction (MI). We evaluated the potency of menstrual blood stromal (stem) cells (MenSCs) and bone marrow stem cells (BMSCs) to alleviate remote organ injuries following MI in rats.Materials and Methods: 2 × 106 MenSCs or BMSCs were administrated seven days after MI induction via the tail vein. Four weeks after cell therapy, activities of aspartate aminotransferase (AST), urea, creatinine, and Blood Urea Nitrogen (BUN) were evaluated. The level of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6 were determined by ELISA assay. The expression of Nuclear Factor-κB (NF-κB) was evaluated by immunohistochemical staining. Apoptosis activity and tissue damage were also determined by TUNEL and H&E staining, respectively.Results: MenSCs and BMSCs administration caused a significant reduction in AST, urea, and BUN levels compared with the MI group. In addition, systemic injection of MenSCs significantly decreased the IL-1β level compared with BMSCs and MI groups (P0.05).Conclusion: MenSCs are probably more protective than BMSCs on remote organ injuries following MI via decreasing cell death and immunoregulatory properties.

Aim: This study was performed to evaluate neural regenerative capacities of bone marrow stem cells (BMSCs) with or without superparamagnetic iron oxide nanoparticles (SPIONs) as a magnetic targeting tool after neurolysis of the facial nerve (FN) in albino rats. Methods: Thirty-eight male albino rats were selected. Two of them were euthanized for normal FN histology assessment. Thirty-six rats were injected with ethanol in the FN nerve for neurolysis induction and assessed one week post-operatively by eye blinking test. Animals were divided into three groups, each containing twelve rats: Group I (positive control) was injected with Dulbecco Modified Eagle's medium (DMEM-F12), group II was injected with BMSCs in DMEM-F12, and group III was injected with BMSCs in DMEM-F12 with poly l-lysine coated SPIONs (0.5 mmol/mL). Monitoring of SPIONs in the rat's body was carried out by MRI. A circular neodymium magnet N52 (0.57 T, 2 × 5 mm) was placed on each rat in group III just below the right ear at the site of surgery to attract SPIONs labeled BMSCs, left in place for 24 h, and then removed. From each group, six rats were euthanized at the end of the 4th and 8th week of treatment, respectively. The right FN trunks were extracted for routine histological examination using H&E stain. Immunohistochemical examination by anti-S100B was performed to characterize the thickness of the myelin sheath formed by the Schwann cells. Ultra-structural examination was performed to study changes in axons, myelin sheaths, and Schwann cells. Results: Regeneration of nerve fibers, Schwan cells, and myelin sheaths was better in group II than in groups I and III histologically, immunohistochemically, and ultra-structurally. Conclusion: BMSCs alone could ameliorate FN regeneration better than magnetic targeting treatment using BMSCs labeled with SPIONs.

Mesenchymal stem cells: they have received great attention in the field of regenerative medicine due to their ability to differentiate into different cell types and their ability to secrete a wide range of biologically active molecules that repair and regenerate tissues. Stem cells are usually isolated from bone marrow, adipose tissue, or other adult tissues and can be grown in culture media to generate large numbers of cells. Stem cells are widely used in veterinary medicine: for the treatment of bone diseases, diseases of the respiratory and digestive systems, immune diseases. The therapeutic effect of stem cells is due to the anti-inflammatory and immunomodulatory effects of the cells themselves and their excretory products. In general, the continuous investigation and development of Veterinary key therapies is essential to improve animal health and well-being, promote Translational Medicine, and thereby benefit human health. Mesenchymal stem cells have been studied as a potential treatment for various gastrointestinal diseases in cattle, including inflammatory bowel disease and Colitis. Stem cells can be used to replace damaged or diseased tissue by differentiating between specific cell types required for repair and regeneration. Stem cells can also secrete factors that promote tissue regeneration, which can enhance their therapeutic potential. Diverse alternatives provide an attractive option for the possibility of developing clinical applications of stem cells in veterinary medicine.

Mesenchymal stem cells: they have received great attention in the field of regenerative medicine due to their ability to differentiate into different cell types and their ability to secrete a wide range of biologically active molecules that repair and regenerate tissues. Stem cells are usually isolated from bone marrow, adipose tissue, or other adult tissues and can be grown in culture media to generate large numbers of cells. Stem cells are widely used in veterinary medicine: for the treatment of bone diseases, diseases of the respiratory and digestive systems, immune diseases. The therapeutic effect of stem cells is due to the anti-inflammatory and immunomodulatory effects of the cells themselves and their excretory products. In general, the continuous investigation and development of Veterinary key therapies is essential to improve animal health and well-being, promote Translational Medicine, and thereby benefit human health. Mesenchymal stem cells have been studied as a potential treatment for various gastrointestinal diseases in cattle, including inflammatory bowel disease and Colitis. Stem cells can be used to replace damaged or diseased tissue by differentiating between specific cell types required for repair and regeneration. Stem cells can also secrete factors that promote tissue regeneration, which can enhance their therapeutic potential. Diverse alternatives provide an attractive option for the possibility of developing clinical applications of stem cells in veterinary medicine. [ABSTRACT FROM AUTHOR]

Objective(s): Remote organ injury is a phenomenon that could happen following myocardial infarction (MI). We evaluated the potency of menstrual blood stromal (stem) cells (MenSCs) and bone marrow stem cells (BMSCs) to alleviate remote organ injuries following MI in rats. Materials and Methods: 2 × 106 MenSCs or BMSCs were administrated seven days after MI induction via the tail vein. Four weeks after cell therapy, activities of aspartate aminotransferase (AST), urea, creatinine, and Blood Urea Nitrogen (BUN) were evaluated. The level of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6 were determined by ELISA assay. The expression of Nuclear Factor-κB (NF-κB) was evaluated by immunohistochemical staining. Apoptosis activity and tissue damage were also determined by TUNEL and H&E staining, respectively. Results: MenSCs and BMSCs administration caused a significant reduction in AST, urea, and BUN levels compared with the MI group. In addition, systemic injection of MenSCs significantly decreased the IL-1β level compared with BMSCs and MI groups (P<0.05 and P<0.01 respectively). Apoptosis in injured kidneys was noticeably diminished in MenSCs-treated rats compared with BMSCs administrated and MI groups (P<0.05 and P<0.05, respectively). In hepatic tissue, limited numbers of TUNEL-positive cells were detected in all groups. Interestingly, MenSCs therapy evoked inhibition of NF-κB in the kidney strikingly. Although, no significant NF-κB expression was observed in hepatic tissue in any group (P>0.05). Conclusion: MenSCs are probably more protective than BMSCs on remote organ injuries following MI via decreasing cell death and immunoregulatory properties. [ABSTRACT FROM AUTHOR]

As a kind of pluripotent stem cells, bone marrow mesenchymal stem cells mainly differentiate into osteoblasts and adipocytes in the bone marrow microenvironment. This mutual restriction and interaction are summarized as bone-fat balance. This dynamic balance plays a crucial role in the maintenance of bone homeostasis. In the process of bone-fat interaction, bone marrow adipose tissue is an important carrier and key pathway for communicating the signals, and mediates various metabolic regulatory processes in the bone marrow microenvironment. In recent years, with the in-depth study of bone-fat metabolism, the related regulatory network of osteoporosis prevention and treatment has been gradually revealed. However, there is still a lack of systematic explanation for the differentiation state and molecular mechanism of bone-fat under physiological and pathological conditions. Therefore, this study intends to analyze the molecular mechanism of bone-fat balance in the perspective of bone marrow microenvironment by summarizing relevant literature and combining our research, in order to provide new ideas for the prevention and treatment of osteoporosis. [ABSTRACT FROM AUTHOR]

Purpose: Numerous studies have described the effect of Electromagnetic Fields (EMFs) in the promotion of Bone Marrow Stem Cell (BMSC) differentiation. We aimed to investigate the influence of frequency (10 and 100 Hz) and different pulse shapes (sine, rectangular, and triangular) of EMF on rats' BMSCs. Materials and Methods: The BMSCs in 6 groups were exposed to EMF for 1 h/ 7 days. The BMSCs viability was estimated by the MTT test. The cresyl violet labeled the Nissl bodies, and the silver nitrate staining was done to evaluate the BMSCs nucleoli Ag Nucleolar Organizer Regions (AgNORs). Results: The MTT test verified that EMF and pulse shape did not affect cell viability. In Nissl bodies staining most of the large neurons were related to the rectangular 10 Hz EMF group. The majority of the differentiated BMSCs were astrocytes, microglia, and oligodendrocyte in the triangular 100 Hz EMF group. Although the silver nitrate staining confirmed the effect of 10 Hz EMF, pulse shape alteration did not affect AgNOR parameters. In conclusion, we presented a low-magnetic flux density EMF (400 µT) to assess the responses of BMSCs nuclei. Conclusion: The findings showed that BMSCs differentiation was frequency-dependent. Further investigations are recommended for recognizing the function of EMF on BMSCs.

Collagen, a natural biomaterial derived from animal tissues, has attracted the attention of biomedical material researchers because of its excellent cell affinity and low rejection in vivo. In this study, collagen was extracted using livestock by-product flippers, and an experiment was performed to assess its application as a scaffold for bone tissue implantation. For this purpose, we fabricated 2%, and 3% duck's feet derived collagen (DC) sponges. We then compared them to hydroxyapatite (HAp)-coated DC sponges, and measured the porosity and pore size using scanning electron microscopy (SEM) to analyze the physical properties and morphology of DC and DC/HAp sponges. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay were carried out to measure the proliferation of bone marrow stem cells (BMSCs) in DC and DC/HAp sponges. An alkaline phosphatase activity assay confirmed the osteogenic differentiation ability of BMSCs. Polymerase chain reaction (PCR) was performed to confirm the BMSC-specific genetic marker. The osteogenic potential was confirmed by the bone formation in an in vivo environment on the scaffold by histological and immunohistochemical analysis. Overall, this study shows that DC/HAp sponges have biocompatibility and good physical properties. Additionally, DC/HAp sponges show potential use as bone graft materials for tissue engineering applications. [ABSTRACT FROM AUTHOR]

Copyright of Journal of China Medical University is the property of Journal of China Medical University Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective: Bioresorbable and titanium plates/screws are considered as a standard treatment for fixation of the bone segments of craniofacial area and paying attention to their biocompatibility is an important issue along with other aspects of application. The purpose of the study was to evaluate the cell viability of two types of plate and screw used in maxillofacial surgeries in contact with gingival fibroblasts and bone marrow stem cells. Materials and Methods: In this experimental study after extraction and cultivation of cells from healthy human gingival tissue and alveolar bone of jaw, cytotoxicity of device was evaluated. In direct contact method, samples had near vicinity contact with the both cell lines and in indirect contact method, by-products released, like ions, from samples after 8 weeks were used to assess cytotoxicity. Then cytotoxicity was evaluated on the 2nd, 4th and 6th day with MTS tests and microscopy. The data were analyzed by one-way ANOVA and independent t tests. Results: There was a statistically significant difference between the German plate and screw and all the samples studied on day 6 (P

Abstract Background About 10 million individuals suffer from traumatic brain injury (TBI) each year in the world, which is one of the most serious neurological disorders. The morbidity of TBI is 55.5~6.1/100,000 in China, which takes more costing in the therapy, and the outcome of that is not well. Therefore, we expect to find new methods to treat TBI and improve the outcomes of TBI. In the previous studies reviewed, we found that stem cell transplantation may hold promising potential for modifying motor dysfunction induced by TBI. Methods Twenty-six adult SD rats were involved in our study. Two adult SD rats were used as donors of bone marrow stem cells (BMSCs), and the other adult SD rats were divided into four groups randomly, which were used to establish the TBI models. BMSCs were transduced with lentivirous-Sox2, and we try to examine the effects of Sox2 on the differentiation of BMSCs. Establishment of rat TBI model Rats were anesthetized using pentobarbital sodium (at a concentration of 1.5% and a dose of 40 mg/kg) and fixed under the stereotaxic device. A 1.0-cm craniotomy was performed lateral to the sagittal suture. The skullcap was carefully removed, and rats were then subjected to TBI using a controlled cortical injury instrument. A standardized parietal contusion was performed using a 20-mg steel rod with a diameter of 4 mm, which dropped from a height of 30 cm. After injury, the incision was sutured, and rats were carefully observed and nursed. Treatments Seven days after TBI, rats were divided into four groups and were transplanted with BMSC-Sox2, single BMSC, single Lentivirus-Sox2, and PBS into injured brain, respectively. The motor function was tested using the neurological severity score (NSS). Results We found that the ectopic expression of Sox2 enhanced BMSCs to differentiate into neurons. Seven days after TBI, the rats were treated with BMSC-Sox2, BMSC, Sox2, and PBS. Results showed that NSS were 3.352 ± 0.398 in the BMSC-Sox2 group, 4.013 ± 0.495 in the BMSC group, 4.968 ± 0.293 in the Sox2 group, and 6.257 ± 0.361 in the PBS group, suggesting that there were obvious improvements in the neurological function in BMSC-Sox2, BMSC, and Sox2 groups. In addition, the BMSC-Sox2 group had the lowest scores, p

Stem cell transplantation is a promising method in the treatment of spinal cord injury (SCI). Researches have shown that stem cell-derived exosomes as well as its contents such as microRNAs contribute to the protective effects of stem cell against SCI. However, the effects of exosomes derived from bone marrow stem cells on SCI and the underlying mechanisms remain unknown. In this study, we collected bone marrow stem cells derived exosomes (BMSCs-exo) to deal with SCI rats and LPS induced microglia to explore the possible mechanisms. We found that BMSCs-exo showed significant effects on decreasing pro-inflammatory cytokines as well as increasing Basso–Beattie–Bresnahan score after acute SCI. MicroRNA-181c levels in tissue were elevated with the use of BMSCs-exo. Then we verified the effect in vitro and found that in LPS induced microglia, the administration of BMSCs-exo could inhibit the expression of pro-inflammatory cytokines, and the phosphorylation of NF-κB signal was also suppressed. During which, the expression of microRNA-181c in microglia was elevated. When LPS induced microglia were treated with BMSCs-exo over-expressing microRNA-181c, the levels of pro-inflammatory cytokines decreased. Then bioinformatics techniques were used to detect the possible target gene of microRNA-181c and then PTEN was found as a candidate. Further experiments showed that the protection effects of BMSCs-exo over-expressing microRNA-181c could be antagonized by the elevation of PTEN expression both in vitro and in vivo. In conclusion, we verified that BMSCs-exo could protect against SCI through its content microRNA-181c which suppressed the inflammation in microglia and spinal cord. It was related to the inhibition of PTEN and the suppression of NF-κB signal, and finally decreasing inflammation and apoptosis in spinal cord and improved SCI. [ABSTRACT FROM AUTHOR]

Introduction: Spinal cord injury (SCI) is a debilitating disease. Bone marrow stem cells (BMSCs) have a high potential to regenerate the nerve lesion but have low survival. The use of artificial scaffolds to increase the survival of cells and strengthen their effects had not good results due to the lack of biologically active substances and the effects of immunogenicity and biocompatibility. The extracellular matrix of natural tissue is a good candidate to overcome these problems. The purpose of this research was using the natural adipose tissue extracellular matrix (AdECM) to enhance the regenerative effects of BMSCs in rat spinal cord injury. Methods and Materials: Extracellular matrix were extracted from rat abdominal fat tissue by physical-chemical method. Then it was converted into a hydrogel using pepsin. Bone marrow stem cells from rat femur extracted and cultured, third passage used for the experiment. One week after the creation of contusion model spinal cord lesion in rats, 10 µl of AdECM hydrogel and one million BMSCs were injected in the spinal cord lesion area. Then the animals were evaluated by behavioral tests for 8 weeks. At the end of the eighth week, an electrophysiological examination was performed and spinal cord tissue samples were extracted, stained and histologically performed on them. Results: The findings showed that AdECM strengthens the regenerative effects of BMSCs. These effects include further reduction of histological signs of spinal cord injury, increase in GAP43 protein expression and enhancement of sensory and motor recovery in rats. Conclusion: These findings suggest that AdECM is a useful natural scaffold for efficient treatment of spinal cord injury. [ABSTRACT FROM AUTHOR]

Background: Angiogenesis is an essential step in tissue engineering. MSC exosomes play an important role in angiogenesis. Functional biomolecules in exosomes vested by the culture microenvironment can be transferred to recipient cells and affects their effect. 3D culture can improve the proliferation and activity of MSCs. However, whether exosomes derived from 3D culture of MSCs have an enhanced effect on angiogenesis is unclear. Methods: Herein, we compared the bioactivity of exosomes produced by conventional 2D culture (2D-exos) and 3D culture (3D-exos) of bone marrow stem cells (BMSCs) in angiogenesis. Results: A series of in vitro and in vivo experiments indicated that 3D-exos exhibited stronger effects on HUVEC cell proliferation, migration, tube formation, and in vivo angiogenesis compared with 2D-exos. Moreover, the superiority of 3D-exos might be attributed to the activation of HMGB1/AKT signaling. Conclusions: These results indicate that exosomes from 3D culture of MSCs may serve as a potential therapeutic approach for pro-angiogenesis.

Copyright of Journal of China Medical University is the property of Journal of China Medical University Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Stem cells are used in cardiovascular biology and biomedicine, and research in this field is expanding. Two types of stem cells have been used in research: induced pluripotent and somatic stem cells. Stem cell research in cardiovascular medicine has developed rapidly following the discovery of different types of stem cells. Induced pluripotent stem cells (iPSCs) possess potent differentiation ability, unlike somatic stem cells, and have been postulated for a long time. However, differentiating into adult-type mature and functional cardiac myocytes (CMs) remains difficult. Bone marrow stem/stromal cells (BMSCs), adipose-derived stem cells (ASCs), and cardiac stem cells (CSCs) are somatic stem cells used for cardiac regeneration. Among somatic stem cells, bone marrow stem/stromal cells (BMSCs) were the first to be discovered and are relatively well-characterized. BMSCs were once thought to have differentiation ability in infarcted areas of the heart, but it has been identified that paracrine cytokines and micro-RNAs derived from BMSCs contributed to that effect. Moreover, vesicles and exosomes from these cells have similar effects and are effective in cardiac repair. The molecular signature of exosomes can also be used for diagnostics because exosomes have the characteristics of their origin cells. Cardiac stem cells (CSCs) differentiate into cardiomyocytes, smooth muscle cells, and endothelial cells, and supply cardiomyocytes during myocardial infarction by differentiating into newly formed cardiomyocytes. Stem cell niches and inflammatory cells play important roles in stem cell regulation and the recovery of damaged tissues. In particular, chemokines can contribute to the communication between inflammatory cells and stem cells. In this review, we present the current status of this exciting and promising research field.

Previous attempts have indicated that mesenchymal stem cells (MSCs) are a valuable source and candidate and new approach for tissue engineering and reproductive medicine. MSCs have this potential to be induced and differentiated in an appropriate in vivo and in vitro condition toward various cell lineages and then they can be applied in cell therapies and clinical applications. During recent two decades, various sources have demonstrated they are a great source for MSCs, including bone marrow, the human umbilical cord as well as Wharton's jelly. Due to discarding after birth, easily accessible cells and less ethical concerns, these cells have attracted more and more scientists' attention. Infertility and reproduction diseases have provided special opportunity to examine the efficiency of MSCs in this kind of application. Based on recent investigations, MSCs embedded in Wharton's jelly tissue are more appealing for cell therapies, especially in infertility treatment purposes. So, differentiation of MSCs embedded in Wharton's jelly tissue into germ layer cells for cell-based therapy purposes is now under intensive study.

Mesenchymal stem cell therapy brings hope for regenerating damaged periodontal tissues. The present study aimed to investigate the therapeutic role of local bone marrow stem cell (BMSC) injection in ligation‐induced periodontitis and the underlying mechanisms. Alveolar bone lesion was induced by placing ligatures subgingivally around the bilateral maxillary second molars for 28 days. The alveolar bone lesion was confirmed by micro‐CT analysis and bone histomorphometry. Allogeneic BMSC transplantation was carried out at 28 day after ligation. The survival state of the transplanted BMSC was observed by bioluminescent imaging. The implantation of the BMSC into the gingival tissues and periodontal ligament was confirmed by green fluorescent protein (GFP) immunohistochemical staining. The expression level of pro‐inflammatory, tumour necrosis factor‐α (TNF‐α) and interleukin‐1β (IL‐1β), and receptor activator of nuclear factor‐κ B ligand (RANKL) and osteoprotegerin (OPG) in periodontal tissues were evaluated by immunohistochemical staining and real‐time PCR. Significant reverse of alveolar bone lesion was observed after BMSC transplantation. The expression of TNF‐α and IL‐1β was down‐regulated by BMSC transplantation. The number of tartrate‐resistant acid phosphatase (TRAP)‐positive osteoclasts in the periodontal ligament was reduced, and the increased RANKL expression and decreased OPG expression were also reversed after BMSC transplantation. It is concluded that allogeneic BMSC local injection could inhibit the inflammation of the periodontitis tissue and promote periodontal tissue regeneration. [ABSTRACT FROM AUTHOR]

Objective: Bioresorbable and titanium plates/screws are considered as a standard treatment for fixation of the bone segments of craniofacial area and paying attention to their biocompatibility is an important issue along with other aspects of application. The purpose of the study was to evaluate the cell viability of two types of plate and screw used in maxillofacial surgeries in contact with gingival fibroblasts and bone marrow stem cells. Materials and Methods: In this experimental study after extraction and cultivation of cells from healthy human gingival tissue and alveolar bone of jaw, cytotoxicity of device was evaluated. In direct contact method, samples had near vicinity contact with the both cell lines and in indirect contact method, by-products released, like ions, from samples after 8 weeks were used to assess cytotoxicity. Then cytotoxicity was evaluated on the 2nd, 4th and 6th day with MTS tests and microscopy. The data were analyzed by one-way ANOVA and independent t tests. Results: There was a statistically significant difference between the German plate and screw and all the samples studied on day 6 (P<0.05). Furthermore, a statistically significant difference was observed between both metal samples and both bio-absorbable samples on day 6 and both cell lines (P<0.05). Comparisons between the two groups with each other for both cell lines on the 6th day were statistically significant (P<0.05). Conclusion: Our results suggest that that cytotoxicity of biomaterial, from different brands, were not similar and some of the biomaterial showed lower degree of toxicity compared to others and specialist using these products showed be aware of this differences. Our investigation indicates more biocompatibility of bioresorbable plates and screws compared to titanium. In addition our results suggest that biomaterials were not completely neutral. [ABSTRACT FROM AUTHOR]

Objective: To investigate the role of HIF1-a in the stem cell differentiation and cell protective effect of curcumin. Methods: Mouse bone marrow mesenchymal stem cells (MSCs) were pretreated with increasing concentrations of curcumin (0.5-20 µ M) f or 1 h our, then 4 00 µ M h ydrogen p eroxide (H2O2) stress was applied and cell viability was measured by MTT test at 24 h. The amount of reactive oxygen species (ROS) was determined by H2DCFDA staining. Alizarin red dye was used to determine the effects of curcumin on cell differentiation. HIF1-a gene expression levels were determined using qRT-PCR. Results: Increasing concentrations of curcumin had no effect on cell viability (p> 0.05). The cell viability of MSCs pretreated with 0.5 µM curcumin for 1 hour increased compared to cells treated with only 400 µM H2O2 (p<0.05). In the curcumin pretreatment group, the amount of ROS was found to be significantly reduced and cell differentiation levels were increased (p<0.05). The amount of HIF1-a m RNA l evels w ere f ound t o be decreased by 1 .86 a nd 2.24 f old, respectively in 0.5 µM and 1 µM curcumin pretreated cells (p <0.05). Conclusion: In this study, it has been shown that curcumin has a protective effect on MSCs. It is thought that treating MSCs with curcumin before they are put into the transplantation media with high levels of ROS will not only maintain the vitality of MSCs, but also help to preserve the therapeutic properties of the cells. [ABSTRACT FROM AUTHOR]

OBJECTIVE: We aimed to evaluate the efficacy of the treatment of knee osteoarthritis (OA) patients by using microfracture technique in combination with autologous bone marrow stem cell transplantation. METHODS: A clinical study was conducted between November 2011 and January 2015 and involved 46 patients (aged from 46 to 69) with primary knee OA grade II and III (according to Kellgren-Lawrence classification) at the Orthopedic Trauma Department, Vietnam-Germany Friendship Hospital. Patients were randomly assigned to receive knee arthroscopy and then bone-marrow stem cells from their pelvic bones via injection. RESULTS: The mean Visual Analogue Scale (VAS) score of present pain decreased from 5.68 before surgery to 1.7 24 months after surgery. The mean preoperative Knee Injury and Osteoarthritis Outcome Score (KOOS) was 36.34 (± 3.13), which increased to 74.62 (± 2.86) 24 months after surgery. On the MRI scans, the average Noyes score decreased from 12 (± 1.46) to 7 (± 1.50). Cartilage volume increased on average from 0.4512 (± 0.26) cm 3 to 0.5463 (± 0.29) cm 3 12–24 months after surgery. CONCLUSION: Treatment of osteoarthritis by a combination of arthroscopic microfracture and transplantation of autologous bone-marrow stem cells was an invasive, safe and effective method which showed an improvement in the clinical symptoms (VAS score) and knee functions (KOOS points). [ABSTRACT FROM AUTHOR]

MG53 is an important membrane repair protein and partially protects bone marrow multipotent adult progenitor cells (MAPCs) against oxidized low‐density lipoprotein (ox‐LDL). The present study was to test the hypothesis that the limited protective effect of MG53 on MAPCs was due to ox‐LDL‐induced reduction of MG53. MAPCs were cultured with and without ox‐LDL (0‐20 μg/mL) for up to 48 hours with or without MG53 and antioxidant N‐acetylcysteine (NAC). Serum MG53 level was measured in ox‐LDL‐treated mice with or without NAC treatment. Ox‐LDL induced significant membrane damage and substantially impaired MAPC survival with selective inhibition of Akt phosphorylation. NAC treatment effectively prevented ox‐LDL‐induced reduction of Akt phosphorylation without protecting MAPCs against ox‐LDL. While having no effect on Akt phosphorylation, MG53 significantly decreased ox‐LDL‐induced membrane damage and partially improved the survival, proliferation and apoptosis of MAPCs in vitro. Ox‐LDL significantly decreased MG53 level in vitro and serum MG53 level in vivo without changing MG53 clearance. NAC treatment prevented ox‐LDL‐induced MG53 reduction both in vitro and in vivo. Combined NAC and MG53 treatment significantly improved MAPC survival against ox‐LDL. These data suggested that NAC enhanced the protective effect of MG53 on MAPCs against ox‐LDL through preventing ox‐LDL‐induced reduction of MG53. [ABSTRACT FROM AUTHOR]

Copyright of Journal of China Medical University is the property of Journal of China Medical University Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Aim: This study was performed to evaluate neural regenerative capacities of bone marrow stem cells (BMSCs) with or without superparamagnetic iron oxide nanoparticles (SPIONs) as a magnetic targeting tool after neurolysis of the facial nerve (FN) in albino rats., Methods: Thirty-eight male albino rats were selected. Two of them were euthanized for normal FN histology assessment. Thirty-six rats were injected with ethanol in the FN nerve for neurolysis induction and assessed one week post-operatively by eye blinking test. Animals were divided into three groups, each containing twelve rats: Group I (positive control) was injected with Dulbecco Modified Eagle's medium (DMEM-F12), group II was injected with BMSCs in DMEM-F12, and group III was injected with BMSCs in DMEM-F12 with poly l-lysine coated SPIONs (0.5 mmol/mL). Monitoring of SPIONs in the rat's body was carried out by MRI. A circular neodymium magnet N52 (0.57 T, 2 × 5 mm) was placed on each rat in group III just below the right ear at the site of surgery to attract SPIONs labeled BMSCs, left in place for 24 h, and then removed. From each group, six rats were euthanized at the end of the 4th and 8th week of treatment, respectively. The right FN trunks were extracted for routine histological examination using H&E stain. Immunohistochemical examination by anti-S100B was performed to characterize the thickness of the myelin sheath formed by the Schwann cells. Ultra-structural examination was performed to study changes in axons, myelin sheaths, and Schwann cells., Results: Regeneration of nerve fibers, Schwan cells, and myelin sheaths was better in group II than in groups I and III histologically, immunohistochemically, and ultra-structurally., Conclusion: BMSCs alone could ameliorate FN regeneration better than magnetic targeting treatment using BMSCs labeled with SPIONs., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Bone marrow stem cells (BMSCs) are a group cells that function as an underlying cell source for bone tissue regeneration. However, the molecular mechanisms of how BMSCs are induced into apoptosis remains unclear. In the present study, it was demonstrated that the molecular mechanisms of BMSCs were exerted via microRNA-15a-5p (miR-15a-5p) in femoral head necrosis (FHN). Briefly, miRNA-15a-5p expression was elevated in a rat model of FHN. Overexpression of miR-15a-5p promoted the apoptosis of BMSCs and reduced cell growth through the Wnt/β-catenin/peroxisome proliferator-activated receptor γ (PPARγ) signaling pathway. Downregulation of miR-15a-5p reduced the apoptosis of BMSCs and promoted cell growth through the Wnt/β-catenin/PPARγ signaling pathway. The activation of Wnt attenuated the effects of miR-15a-5p on the apoptosis of BMSCs via the β-catenin/PPARγ signaling pathway. In conclusion, the present results indicated that miRNA-15a-5p was involved in the regulation of the apoptosis of BMSCs through regulating the Wnt/β-catenin/PPARγ signaling pathway, which may serve an important role in the regulation of FHN. [ABSTRACT FROM AUTHOR]

To investigate the impact of different anticoagulants and coagulants with autologous platelet-rich plasma (PRP) in order to evaluate the clinical application of PRP standardization. Bone marrow stem cells (BMSCs) were seeded into autologous PRP gel scaffolds with different anticoagulants (EDTA, heparin sodium HS, and sodium citrate SC) as well as control group (the whole blood group). Quality of PRP was evaluated and flow cytometric assay was used to detect the activity of the platelet (CD62p, PAC-1). BMSCs were also seeded into PRP with different coagulants (Thrombin, Collagen-I, ADP) as well as PRP un-activated (negative group) and L-DMEM complete culture without PRP (control group). The effects of different coagulants with PRP on proliferation, osteogenic differentiation of BMSCs were analyzed by methyl thiazolyl tetrazolium assay (MTT), ALP staining, Von Kossa staining, Confocal microscopic observation, RT-PCR and Western Blot at the morphological, cellular and molecular levels. Different anticoagulants (EDTA, HS, and SC) could affect the quality of PRP. EDTA group revealed the best quality and activity (CD62p, PAC-1). With different coagulants (Thrombin, Collagen-I and ADP) in the proliferation of BMSCs, the MTT assay showed that the proliferation of BMSCs was increased in all groups with time. On the sixth day of culture, the cell number of each PRP group was significantly higher than that in the control group (P < 0.05), while the most rapidly increasing was found in Collagen-I group. The cumulative release of growth factor (TGF-β1, PDGF) at each time point in the PRP gel of the four groups was higher than that in the control group (P < 0.05). Collagen-I was considered as the best PRP coagulant. When thrombin was used as a platelet coagulant, the release of growth factor in PRP was rapid and direct, while the release of growth factor in Collagen-I-activated PRP was sustained and slow, and the total release of ADP-activated PRP growth factors was the lowest. The study demonstrated the similar outcome in osteogenic differentiation. In terms of gene expression and western bolt, the PCR results showed that the expression levels of OCN gene and RUNX2 protein in each PRP group were higher than that in the control group (P < 0.05). Different anticoagulants caused different degrees of lysis and spontaneous activation of platelets, which lead to different quality of PRP. Compared with HS and SC, EDTA could maintain the structural integrity of platelets, reduce their spontaneous activation, and increase the release of PRP growth factors for a longer period of time, thus ensuring the biomass of PRP. In addition, different coagulants also showed different results in the proliferation as well as osteogenic differentiation of BMSCs. Compared with Thrombin and ADP, Collagen-I may be a better choice. [ABSTRACT FROM AUTHOR]

Multipotent stem cells (MSCs) are used in various therapeutic applications based on their paracrine secretion activity. Here, we set out to identify and characterize the paracrine factors released during osteoblastogenesis, with a special focus on small non-coding RNAs released in extracellular vesicles (EVs). Bone marrow stem cells (BMSCs) and adipose stem cells (ASCs) from healthy human donors were used as representatives of MSCs. We isolated EVs secreted before and after induction of osteoblastic differentiation and found that the EVs contained a specific subset of microRNAs (miRNAs) and tRNA-derived small RNAs (tsRNA) compared to their parental cells. Osteoblastic differentiation had a larger effect on the small RNA profile of BMSC-EVs relative to ASC-EVs. Our data showed that EVs from different MSC origin exhibited distinct expression profiles of small RNA profiles when undergoing osteoblastogenesis, a factor that should be taken into consideration for stem cell therapy.

Background ― The problem of incomplete myocardial revascularization for diffuse and distal lesions of the myocardium is still relevant. We assessed the clinical and instrumental long-term results of autologous bone marrow cell (BMC) implantation in laser channels in ischemic heart disease with diffuse and distal coronary disease. Material and Methods ― In 2007 and 2008, 35 ischemic heart disease (IHD) patients with diffuse and distal coronary disease during coronary artery bypass grafting (CABG) underwent BMC implantation in laser channels in the clinic of National Medical Research Center n.a. E.N. Meshalkin (Novosibirsk, Russia). This group was named as “BMC group”. The Control group consisted of 29 patients who underwent only CABG. Clinical and instrumental assessment of the method's effect was carried out at two weeks, six months, and six years after surgery. Long-term follow-up was performed only in 30 patients from the BMC group. Results ― After six months postoperatively, the severity of angina and heart failure based on Canadian Cardiovascular Society functional class (CCS FC) and the New York Heart Association functional class (NYHA FC) was significantly less in the BMC group than in the Control group (p=0.03 for CCS FC and p=0.04 for NYHA FC). Six years after surgery angina and heart insufficiency were at the same level. According to perfusion scintigraphy, there was a slight decrease of stable perfusion defects (SPD) in the immediate postoperative period and a more pronounced SPD reduction at six months after surgery. In BMC group, the SPD value before surgery was 18.4 (12.8, 22.4) %, 16.1 (11.6, 19.3) % at two weeks after the operation, and 13.2 (8.5, 17.3) % after six months. In the long-term period (six years), SPD was 11.9 (8.7, 14.2) % (p=0.047). A similar pattern was observed in the analysis of transient perfusion defects: baseline was 29.3 (22.1, 34.1) %, 13.1 (11.2, 16.5) % at six months, and 17.0 (14.3, 20.5) % in the long term (p=0.047). Left ventricular ejection fraction before surgery was 51 (49, 57) %, 54 (49, 57) % at two weeks after the operation, 54 (49, 58) % at six months, and 52 (49, 58) % after six years. The dynamics are not statistically significant (p=0.068). Conclusion ― Autologous BMC implantation in laser channels is an effective method of IHD surgical treatment if it is impossible to perform direct myocardial revascularization. The indirect revascularization effect is formed in the first six months after surgery and remains at the same level for six years.

The objective of this study was to evaluate the effect of bone marrow stem cells (BMSCs)‐seeded polyethylene terephthalate (PET) scaffold for Achilles tendon repair in a rabbit model. The allogeneic BMSCs were seeded onto the PET scaffold and cultured in vitro for 14 days. Sixteen mature New Zealand rabbits underwent surgery to establish a 2‐cm Achilles tendon defect model. The BMSCs‐seeded PET scaffold was implanted into the defect of one limb (BMSCs‐PET group), while the PET scaffold without BMSCs was implanted into the defect of contralateral limb as the control (PET group). All rabbits were sacrificed at 6 and 12 weeks after surgery. At 12 weeks after surgery, macroscopic and histological results showed formation of tendon‐like tissues, and the structure was more mature in the BMSCs‐PET group. Immunohistochemical analysis and real‐time polymerase chain reaction (RT‐PCR) demonstrated that the collagen I and collagen III were significantly higher in the BMSCs‐PET group compared with those in the PET group. Mechanically, both the failure load and the average stiffness were significantly higher in the BMSCs‐PET group than those in the PET group. In conclusion, BMSCs‐seeded PET scaffold could effectively facilitate the healing process after being implanted in a rabbit Achilles tendon defect model. [ABSTRACT FROM AUTHOR]

Abstract: To investigate the potential beneficial effect of insulin‐like growth factor‐1 (IGF‐1) in BMSC transplantation therapy of uterus injury and the underlying molecular mechanisms, rat BMSCs were isolated and cultured. The relative expressions of IGF‐1 and IL‐10 were determined by RT‐PCR and immunoblotting. The secretory IL‐10 and released E2 were measured using ELISA kits. The relative vWF and α‐SMA expressions were determined by immunohistochemistry. The direct binding of NF‐κB subunit p50 with IL‐10 promoter was analysed by chromatin immunoprecipitation assay. The regulation of IL‐10 expression by p50 was interrogated by luciferase reporter assay. Our data demonstrated that IGF‐1 expression in BMSCs induced IL‐10 expression and secretion, which was further enhanced by E2‐PLGA. IGF‐1 overexpression improved BMSCs transplantation therapy in rat uterus injury. We further demonstrated that both inhibition and knockdown of p50 abolished IGF‐1‐induced expression and secretion of IL‐10 in BMSCs, which consequently compromised the IGF‐1 conferred therapeutic benefits against uterus injury. Furthermore, we elucidated that p50 regulated IL‐10 expression via direct association with its promoter. Our data suggested that transplantation of IGF‐1 overexpressing BMSCs improved functional regeneration of injured uterus by inducing IL‐10 expression and secretion via activation of NF‐κB signalling. [ABSTRACT FROM AUTHOR]

Portal hypertension (PH) is responsible for the most severe complications of cirrhosis and leading cause of death and liver transplantation. The standard pharmacological treatment available for PH currently consists of the use of a non-selective beta-blocker. However, a significant proportion of patients do not respond to pharmacological treatment. This has led to the development of identifiable targets for the discovery of new horizons in PH treatment. Recently, there has been significant progress in understanding the mechanism behind PH, which is a product of increased hepatic vascular resistance including structural changes and functional change due to endothelial dysfunction. Moreover, increased portal inflow is the outcome of dilation of splanchnic vessels and hyperdynamic circulation. Here, challenges in formulating potential pharmacological treatment as well as current potential targets for PH will be reviewed. During the past decades, there have been many efforts to explore new techniques to stimulate liver regeneration in addition to pharmacological treatment. The bone marrow (BM) stem cells which differentiate into mature hepatocytes are thought to contribute to liver regeneration and have been found to demonstrate great potential as regenerative medicine in different therapeutic applications. Based on these insights, we explore the current and potential novel therapeutic uses of BM stem cell therapy in PH. [ABSTRACT FROM AUTHOR]

We prepared in situ gelling alginate (ALG)/hyaluronic acid (HA) hydrogels with a controllable gelation rate using CaSO 4 as a crosslinking agent and Na 2 HPO 4 as a crosslinking retardation agent. The ALG/HA hydrogels provided sustained release of bone morphogenetic protein-2 (BMP-2) immobilized in the hydrogels over 5 weeks. The BMP-2-immobilized ALG/HA hydrogels with different ALG/HA ratios were investigated for their in vitro osteogenic differentiation behavior of human bone marrow stem cells ( h BMSCs) and in vivo bone regeneration behavior using an animal model (mandibular defect model of miniature pigs). Our findings from cell culture and animal study demonstrated that the osteogenic differentiation of h BMSCs was improved with increasing HA composition in the hydrogel. The h BMSCs/BMP-2-immobilized ALG/HA hydrogel allowed greatly enhanced osteogenic differentiation of h BMSCs ( in vitro ) and bone regeneration ( in vivo ) compared with the ALG/HA hydrogel itself and single hBMSCs- or BMP-2-immobilized hydrogel groups. [ABSTRACT FROM AUTHOR]