Mesenchymal Stem Cell Transplantation Research Articles

Changes in the macrophage polarization in the kidneys of rats with acute respiratory distress syndrome after transplantation of human umbilical cord-derived mesenchymal stem cell

Acute respiratory distress syndrome (ARDS) is a critical state of the body characterized by severe hypoxemia and multiple organ failure. One of the organs that is most often additionally affected due to the systemic inflammatory reaction that occurs in the lungs during ARDS is the kidney. It is known that mesenchymal stem cells (MSCs) can exhibit nephroprotective effects due to their anti-inflammatory and immunomodulatory abilities, but the mechanisms of such therapeutic effects require further elucidation. The purpose is to analyze macrophage polarization in the damaged kidneys of rats with modeled ARDS following the transplantation of human umbilical cord-derived MSCs. Materials and methods. Seventy-two sexually mature male Wistar rats were randomly divided into nine groups: intact animals, 3 days, 7 days and 28 days after ARDS modeling, control-MSC and four correction groups: 24 h ARDS + 2 days MSCs, 4 days of ARDS + 3 days of MSCs, 14 days of ARDS + 14 days of MSCs, 21 days of ARDS + 7 days of MSCs. ARDS was modeled by intranasal administration of lipopolysaccharide (LPS) at a dose of 5 mg/kg. A suspension of MSCs was obtained from the umbilical cord of a healthy donor after a normal delivery by an enzymatic method and administered intraperitoneally at a dose of 1 million cells/kg of body weight. For immunohistochemical determination of the total number of macrophages, pro-inflammatory M1 and anti-inflammatory M2 cells, monoclonal antibodies to CD68, CD86 and CD163 were used, respectively, and the percentage of visual fields occupied by the immunoprecipitate was calculated. Results. Comparative analysis of the percentage of areas occupied by the immunoprecipitate with the corresponding antibodies showed a statistically significant increase in the total number of macrophages (3.8-fold on day 3 of ARDS, 2.8-fold on day 7 of ARDS and 2.4-fold on day 28 of ARDS, respectively), as well as a sharp increase in pro-inflammatory M1 (8.8-fold on day 3 of ARDS, 4.9-fold on day 7 of ARDS, and 4.8-fold on day 28 of ARDS, respectively) and a moderate increase in the percentage of anti-inflammatory M2 cells (1.9-fold on day 3 of ARDS, 2-fold on day 7 of ARDS, and 1.6-fold on day 28 of ARDS, respectively) in modeled ARDS compared to intact animals. This indicates the activation of the inflammatory cascade in the kidneys caused by the development of ARDS. On the other hand, in groups of animals that received MSC correction, a significant decrease, compared to untreated animals, in the total number of macrophages was detected (at 24 h of ARDS + 2 days of MSCs, it was 3.2 times lower than on day 3 of ARDS and ≥ 2 times at later times of the experiment), among which anti-inflammatory cells of the M2 phenotype predominated. Conclusion. Transplanted human umbilical cord-derived MSCs have a pronounced immunomodulatory effect in the affected kidneys of rats with acute respiratory distress syndrome, which is manifested in their ability to change the polarization of macrophages in the anti-inflammatory direction.

Protective effects of puerarin combined with bone marrow mesenchymal stem cells on nerve injury in rats with ischemic stroke

ABSTRACT Background Bone marrow mesenchymal stem cells (BM-MSCs) transplantation shows promise for treating ischemic stroke, but the ischemic environment that follows cerebral infarction hinders the survival of transplanted cells. We aimed to study the effects of puerarin (Pue) in combination with BM-MSCs on cerebral ischemic injury. Methods After middle cerebral artery occlusion (MCAO) models were prepared by suture-occluded method, rats were randomly allocated to the sham, MCAO, Pue (50 mg/kg), BM-MSCs (2×106), and BM-MSCs+Pue groups. The neurological function, infarct area, levels of inflammation-related factors, brain tissue damage, apoptosis, BrdU, Beclin1, and LC3 levels were then assessed. Results Pue and BM-MSCs reduced the modified neurological severity score, cerebral infarction area, and serum inflammation-related factor levels for MCAO rats. Furthermore, Pue and BM-MSCs interventions ameliorated brain tissue damage, and repressed apoptosis of brain tissues in MCAO rats. Moreover, Pue or BM-MSCs enhanced BrdU expression, restrained LC3II/LC3I ratio and Beclin 1 expression in MCAO rats’ brain tissues. Importantly, the combination of Pue and BM-MSCs exhibited more pronounced effects on aforementioned outcomes. Conclusion The combination of Pue and BM-MSCs facilitated the recovery of neurological function in rats after cerebral ischemic damage, and the mechanisms may correlate with the repression of neuronal apoptosis, inflammation, and autophagy.

Autologous Bone Marrow-Derived Mesenchymal Stem Cell Transplantation for Decompensated Post-Hepatitis B Cirrhosis: A Case Report

End-stage liver disease (ESLD) represents the terminal phase of chronic liver injury, characterized by overt clinical manifestations and severe complications that significantly impair the quality of life. The condition often culminates in a variety of symptoms, including jaundice, ascites, and hepatic encephalopathy, which reflect the liver's inability to perform its essential functions. Liver transplantation remains the definitive treatment for ESLD; however, limitations in donor organ availability necessitate exploration of alternative therapeutic strategies. we present a case of a 71-year-old Asian male with decompensated post-hepatitis B cirrhosis, who had a one-year history of hematemesis and melena. Endoscopic evaluation confirmed the presence of esophageal-gastric varices, further corroborating portal hypertension and hypersplenism. This patient underwent treatment with autologous bone marrow-derived mesenchymal stem cell (BM-MSC) transplantation. Following the procedure, the patient demonstrated significant clinical improvement, suggesting the safety and potential feasibility of BM-MSC transplantation for patients with ESLD. The field of BM-MSC transplantation has witnessed significant progress in recent years, emerging as a promising therapeutic approach for ESLD. This innovative treatment modality harnesses the regenerative capabilities of stem cells to promote liver repair and function. Notably, BM-MSCs possess immunomodulatory properties that may mitigate inflammation and fibrosis in the liver, thereby addressing some of the underlying pathophysiology associated with ESLD. This case presentation highlights the potential application of BM-MSC therapy in patients with decompensated cirrhosis. The findings underscore the need for further research and refinement of clinical application techniques to fully realize the broad therapeutic possibilities of BM-MSC transplantation for ESLD. As we advance our understanding of stem cell therapies, it is crucial to conduct larger studies to evaluate long-term outcomes and establish standardized protocols for treatment.

Bilobalide Activates Autophagy and Enhances the Efficacy of Bone Marrow Mesenchymal Stem Cells on Spinal Cord Injury Via Upregulating FMRP to Promote WNK1 mRNA Decay.

Transplantation of bone marrow mesenchymal stem cells (BMSCs) represents an encouraging strategy for the repair of spinal cord injury (SCI), however, its effectiveness on treating SCI remains controversial. Bilobalide isolated from Ginkgo biloba leaves shows significant neuroprotective effects. We examined the role and underlying mechanism of bilobalide in the efficacy of BMSC transplantation on SCI. Primary BMSCs were isolated from neonatal rats, and cell viability was assessed by MTT assay. Neuronal markers (MAP-2, NeuN, NSE and Tuj1), autophagy markers (LC3 and Beclin1), and Fragile X mental retardation protein (FMRP)/With-no-lysine kinase-1 (WNK1) signaling were measured using RT-qPCR and western blotting. The relationship of FMRP and WNK1 was estimated by RNA immunoprecipitation, while WNK1 mRNA stability was assessed with actinomycin D assay. In a SCI rat model, tissue injury was examined using HE and Nissl staining. Bilobalide treatment facilitated neural differentiation of BMSCs, as well as enhanced autophagy and inhibited WNK1 signaling. The promotive effect of bilobalide on BMSC differentiation was antagonized when overexpressing WNK1 or inhibiting autophagy. Bilobalide upregulated FMRP to promote WNK1 mRNA decay, thus reducing WNK1 expression. FMRP knockdown reversed the promoted functions of bilobalide on autophagy and neuronal differentiation in BMSCs. Additionally, compared to either monotherapy, simultaneous treatments with bilobalide and BMSCs further facilitated autophagy and neuronal differentiation, thereby enhancing the repair of SCI in rats. Bilobalide enhances autophagy activity to promote BMSC neuronal differentiation via FMRP/WNK1 axis, thus improving functional recovery following SCI, which indicates a promising therapeutic approach for SCI.

Macrophage tracking with USPIO imaging and T2 mapping predicts immune rejection of transplanted stem cells

To develop a clinical imaging method for monitoring macrophage migration to the defect site after implantation of various stem cells and evaluating immune responses in the context of knee arthritis, T2 mapping was correlated with CD68-positive cell densities in defects and the bone marrow. This study, which was approved by the Institutional Animal Care and Use Committee, used 32 New Zealand white rabbits preloaded with ultrasmall superparamagnetic iron oxide particles (USPIOs). They were divided into groups that received different stem cell implants after osteochondral defect induction. T2 imaging was performed using a 3.0 T MR scanner, and the data were analysed via one-way ANOVA, with CD68 expression assessed via immunohistochemistry. After implantation, the T2 signal intensity increased across groups, with subgroup D1 (implantation of rat bone marrow stem cells (BMSCs)) showing the lowest T2 value early and the steepest increase in T2 values. Notable differences in CD68-positive cell density were found between Subgroup D1 and the other groups and between Subgroups A1 and C1 post-surgery. A moderate negative correlation was observed between T2 signals and CD68-positive cell density in defects (r = -0.468, p = 0.001), whereas a weak correlation was detected in the bone marrow (r = 0.096, p = 0.313). A significant link was identified between CD68-positive cell density in the bone marrow and in defects (r = -0.255, p = 0.001). This study revealed significant differences in immune responses to stem cells from different origin tissues in the context of cartilage repair. Adipose-derived stem cells (ADSCs) were found to be more likely to provoke immune rejection than were BMSCs in the repair of femoral condyle cartilage defects. Compared with allogeneic transplants, xenogeneic mesenchymal stem cell transplants were associated with prolonged immune rejection. T2 mapping technology was effective in predicting the density of CD68-positive cells, providing a valuable tool for immune monitoring in stem cell therapy.

BMSCs transplantation combined with LIPUS treatment improves erectile function through downregulation of IGFBP3 in rats with cavernosa injury.

Erectile dysfunction (ED) is the most common type of sexual dysfunction, which seriously affects male reproductive health. Recently, stem cell therapy and low-intensity pulsed ultrasound (LIPUS) have been applied in the treatment of ED, but the specific mechanism is still unclear. The study aims to investigate the effect and underlying mechanism of further LIPUS treatment on the basis of bone marrow mesenchymal stem cells (BMSCs) transplantation in the treatment of ED rats. We established a cavernosa injury-induced ED rat model and injected BMSCs into the penile corpus cavernosum with or without LIPUS treatment every other day for three times. The survival rate of BMSCs, value of ICP/MAP, blood flow, the endothelial content, and expression of CD31 and ɑ-SMA in the rat penis were investigated. Transcriptome analyses and in vitro assays of cell proliferation, migration, and tube formation were also performed. The results showed that LIPUS treatment significantly promoted the survival rate of BMSCs in the rat penis after 1, 7, and 14 days of final treatment. The values of ICP/MAP and blood flow in rats treated with BMSCs were significantly increased compared to the control group, and the values were further enhanced in rats treated with BMSCs plus LIPUS. The endothelial content and CD31 and ɑ-SMA mRNA and protein expression in the BMSCs plus LIPUS group were remarkably higher than in other groups, indicating improved endothelial vascular function. Transcriptome analyses found that insulin-like growth factor binding protein-3 (IGFBP3) was remarkably downregulated in the BMSCs plus LIPUS group compared to the other two groups. In in vitro assays, LIPUS intervention significantly increased BMSCs proliferation and HUVECs migration, and HUVECs angiogenesis was improved after IGFBP3 siRNA transfection. BMSCs transplantation combined with LIPUS treatment could improve erectile function in ED rats via downregulation of IGFBP3, which might be a proposed optimized strategy for the ED treatment.

Effects of muscle energy technique along conventional physical therapy after mesenchymal stem cell transplantation in knee osteoarthritis patients.

To assess the efficacy of muscle energy technique (MET) in combination with conventional physical therapy compared to conventional physical therapy alone following mesenchymal stem cell transplantation in knee osteoarthritis (OA) patients. A randomized clinical trial was conducted at the Institute of Regenerative Medicine (IRM), Islamabad, Pakistan, for a time duration of 11 months from September 2022 to July 2023. Using non-probability purposive sampling, patients were randomly allocated to two treatment groups. Three treatment sessions per week for two weeks, lasting thirty minutes each, were administered with follow-up after one month. Numerical Pain Rating Scale, Western Ontario and McMaster Universities Arthritis Index, ROM, were used to assess the Pain, functional status, and Range of motion. Within Group-Analysis was done using Friedman with Wilcoxon signed-rank tests, while Mann-Whitney U-tests determined inter-group differences. With-in Group-Analysis, showed statistically significant (p<0.05) at baseline, after one week, after two weeks, and after one month follow up in both the muscle energy technique (MET) Group-And conventional therapy group for NPRS, KNEE FLEXION ROM, and WOMAC. Between-Group-Analysis, also showed significant (p<0.05) for knee pain and WOMAC scores. Both groups are effective for improving knee pain, and functional limitation in knee osteoarthritis patients. However, MET Group along with conventional therapy showed marked effects on improving knee pain, knee flexion ROM, and functional limitations after mesenchymal stem cell transplantation in knee osteoarthritis patients.

Interventional effect of bone marrow mesenchymal stem cell transplantation with different doses of X-ray irradiation induced hepatic injury in mice

Objective: To investigate the interventional effect of bone marrow mesenchymal stem cell (BMMSC) transplantation with different doses of X-ray irradiation induced hepatic injury in mice. Methods: Eighteen female C57BL/6J mice were randomly divided into 0, 2, and 3 Gy irradiation groups and 0, 2, and 3 Gy transplantation groups. The irradiation group was used as the control and injected with an equal volume of culture medium. The mice in the transplantation group were irradiated with different doses of X-ray irradiation, and BMMSCs were intravenously infused into the bone marrow. The mice were sacrificed for sampling at the end of the 21st day. Mice body weight changes were recorded daily. The changes in the content of peripheral blood lymphocytes, red blood cells, platelets, and hemoglobin were detected by an automatic blood tester. The morphological changes in mice liver tissues were observed by hematoxylin-eosin staining. The serum activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected by a biochemical analyzer. The reduced glutathione contents in liver tissue were detected by the microplate method. The malondialdehyde content in liver tissue was detected by thiobarbituric acid. The content of total superoxide dismutase (T-SOD) in liver tissue was detected by the hydroxylamine method. The expression of the F4/80 protein in liver tissue was detected by the immunohistochemistry method. The protein expression of nuclear transcription factor erythroid 2 related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) in liver tissue was determined by the western blotting method. The mRNA expression of NLRP3, IL-6, and Nrf2 in liver tissue was detected by a real-time quantitative polymerase chain reaction. The multiple-group comparisons were analyzed by factorial analysis of variance. The inter-group comparisons were analyzed by the LSD method for statistical analysis. Results: The contents of peripheral blood lymphocytes, erythrocytes, platelets, and hemoglobin were significantly decreased in the 3 Gy irradiation group than the 0 Gy irradiation group (P<0.05), while the activities of serum ALT and AST were significantly increased (P<0.05). The malondialdehyde content, F4/80 protein expression level, nucleotide-binding domain and leucine-rich repeats, nucleotide oligomerization domain-like receptor family, pyrin domain containing 3 (NLRP3), and interleukin 6 mRNA expression levels were significantly increased in liver tissue, while the contents of T-SOD and glutathione, Nrf2 and HO-1 protein expression levels, and Nrf2 mRNA expression level in liver tissue were significantly decreased (P<0.05). The contents of peripheral blood lymphocytes, red blood cells, platelets, and hemoglobin were significantly increased in the 3 Gy transplantation group than the 3 Gy irradiation group (P<0.05), while the activities of serum ALT and AST were significantly decreased (P<0.05). The malondialdehyde content, F4/80 protein expression level, NLRP3 and interleukin-6 mRNA expression levels in liver tissue were significantly decreased (P<0.05), while the content of T-SOD and glutathione, Nrf2 and HO-1 protein expression levels, and Nrf2 mRNA expression level in liver tissue were significantly increased (P<0.05). Conclusion: X-ray irradiation at a dose of 3 Gy can induce liver oxidative damage in mice. BMMSC transplantation can improve X-ray irradiation-induced liver oxidative damage in mice, and its mechanism of action may be related to the regulation of the Nrf2/HO-1 pathway.

Pretreatment with Notoginsenoside R1 enhances the efficacy of neonatal rat mesenchymal stem cell transplantation in model of myocardial infarction through regulating PI3K/Akt/FoxO1 signaling pathways

BackgroundAlthough stem cell transplantation is a promising approach for the treatment of myocardial infarction (MI), there are still some problems faced such as the low survival rate of stem cells. Here, we investigated the role of Notoginsenoside R1 (NGR1) pretreatment in improving the effects of neonatal rat bone marrow mesenchymal stem cell (MSC) transplantation for treatment of MI.MethodsCardiac functions were detected by echocardiography and the myocardial infarct size was determined by Masson’s trichrome staining in a rat model of MI. The cardioprotective effects of NGR1/LY294002 co-pretreated MSCs was evaluated to explore the underlying mechanism. The angiogenesis was determined by vWF and α-SMA immunofluorescence staining and cell apoptosis was detected by TUNEL. In vitro, the effects of NGR1 on stem cell proliferation was examined by CCK-8 and levels of P-Akt, P-CREB, P-FoxO1 were detected by western blot. Apoptosis, ROS content, and cytokine levels were examined by DAPI and TUNEL staining, a ROS assay kit, and ELISA, respectively.ResultsNGR1 elevated the therapeutic effect of MSC transplantation on infarction by preserving cardiac function, increasing angiogenesis and expressions of IGF-1, VEGF, and SDF-1, and reducing cell apoptosis, whereas the addition of LY294002 prior to NGR1 treatment significantly counteracted the foregoing effects of NGR1. NGR1 pretreatment and SC79 pretreatment were similar in that both significantly increased P-Akt and P-FoxO1 levels in MSC and did not affect P-CREB levels. Besides, both NGR1 and SC79 promoted VEGF, SCF and bFGF levels in MSC cultures, and significantly reduced ROS accumulation and the attenuated cell apoptosis in MSC triggered by H2O2. Similarly, addition of LY294002 before NGR1 treatment significantly counteracted the aforementioned effects of NGR1 in vitro.ConclusionsNGR1 pretreatment enhances the effect of MSC transplantation for treatment of MI through paracrine signaling, and the mechanism underlying this effect may be associated with PI3K/Akt/FoxO1 signaling pathways.

Preclinical safety and efficacy evaluation of the intrathecal transplantation of GMP-grade human umbilical cord mesenchymal stem cells for ischemic stroke.

Intrathecal administration of human umbilical cord mesenchymal stem cells may be a promising approach for the treatment of stroke, but its safety, effectiveness, and mechanism remain to be elucidated. In this study, good manufacturing practice-grade human umbilical cord mesenchymal stem cells (5 × 105 and 1 × 106 cells) and saline were administered by cerebellomedullary cistern injection 72 hours after stroke induced by middle cerebral artery occlusion in rats. The results showed (1) no significant difference in mortality or general conditions among the three groups. There was no abnormal differentiation or tumor formation in various organs of rats in any group. (2) Compared with saline-treated animals, those treated with human umbilical cord mesenchymal stem cells showed significant functional recovery and reduced infarct volume, with no significant differences between different human umbilical cord mesenchymal stem cell doses. (3) Human umbilical cord mesenchymal stem cells were found in the ischemic brain after 14 and 28 days of follow-up, and the number of positive cells significantly decreased over time. (4) Neuronal nuclei expression in the human umbilical cord mesenchymal stem cell group was greater than that in the saline group, while glial fibrillary acidic protein and ionized calcium binding adaptor molecule 1 expression levels decreased. (5) Human umbilical cord mesenchymal stem cell treatment increased the number of CD31+ microvessels and doublecortin-positive cells after ischemic stroke. Human umbilical cord mesenchymal stem cells also upregulated the expression of CD31+/Ki67+. (6) At 14 days after intrathecal administration, brain-derived neurotrophic factor expression in the peri-infarct area and the concentrations of brain-derived neurotrophic factor in the cerebrospinal fluid in both human umbilical cord mesenchymal stem cell groups were significantly greater than those in the saline group and persisted until the 28th day. Taken together, these results indicate that the intrathecal administration of human umbilical cord mesenchymal stem cells via cerebellomedullary cistern injection is safe and effective for the treatment of ischemic stroke in rats. The mechanisms may include alleviating the local inflammatory response in the peri-infarct region, promoting neurogenesis and angiogenesis, and enhancing the production of neurotrophic factors.

Human-Brain-Derived Ischemia-Induced Stem Cell Transplantation Is Associated with a Greater Neurological Functional Improvement Compared with Human-Bone Marrow-Derived Mesenchymal Stem Cell Transplantation in Mice After Stroke.

The transplantation of injury/ischemia-induced stem cells (iSCs) extracted from post-stroke human brains can improve the neurological functions of mice after stroke. However, the usefulness of iSCs as an alternative stem cell source remains unclear. The current study aimed to assess the efficacy of iSC and mesenchymal stem cell (MSC) transplantation. In this experiment, equal numbers of human brain-derived iSCs (h-iSCs) (5.0 × 104 cells/μL) and human bone marrow-derived MSCs (h-MSCs) (5.0 × 104 cells/μL) were intracranially transplanted into post-stroke mouse brains after middle cerebral artery occlusion. Results showed that not only h-iSC transplantation but also h-MSC transplantation activated endogenous neural stem/progenitor cells (NSPCs) around the grafted sites and promoted neurological functional improvement. However, mice that received h-iSC transplantation experienced improvement in a higher number of behavioral tasks compared with those that received h-MSC transplantation. To investigate the underlying mechanism, NSPCs extracted from the ischemic areas of post-stroke mouse brains were cocultured with h-iSCs or h-MSCs. After coincubation, NSPCs, h-iSCs, and h-MSCs were selectively collected via fluorescence-activated cell sorting. Next, their traits were analyzed via microarray analysis. The genes related to various neuronal lineages in NSPCs after coincubation with h-iSCs were enriched compared with those in NSPCs after coincubation with h-MSCs. In addition, the gene expression patterns of h-iSCs relative to those of h-MSCs showed that the expression of genes related to synapse formation and neurotransmitter-producing neurons increased more after coincubation with NSPCs. Hence, cell-cell interactions with NSPCs promoted transdifferentiation toward functional neurons predominantly in h-iSCs. In accordance with these findings, immunohistochemistry showed that the number of neuronal networks between NSPCs and h-iSCs was higher than that between NSPCs and h-MSCs. Therefore, compared with h-MSC transplantation, h-iSC transplantation is associated with a higher neurological functional improvement, presumably by more effectively modulating the fates of endogenous NSPCs and grafted h-iSCs themselves.

A comprehensive evaluation system for ultrasound-guided infusion of human umbilical cord-derived MSCs in liver cirrhosis patients.

Infusion of mesenchymal stem cells (MSCs) via portal vein is one of the main ways for MSCs transplantation to treat liver cirrhosis (LC). As the tissue of LC showed diffuse fibrosis and thickened Glission sheath, the soft pig-tail catheter, or central venous catheter can not successfully insert the portal vein. Thus, our study used an improved method and performed a relatively comprehensive system to evaluate the effect for human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) transplantation. Fifteen patients with hepatitis B-related cirrhosis were enrolled in the study, and we performed hUC-MSCs transplantation via portal vein by using an 16-G needle and 0.035-inch guide wire combined with 7FR "retentional metal stiffner trocar" of pig-tail catheter under the guidance of contrast-enhanced ultrasound. Serum liver function, fibrotic indicators, tissue stiffness, coagulation function, and hemodynamics were measured at weeks 4, 12, and 24 after MSCs transplantation. Liver biopsy was performed before and 24 weeks after hUC-MSCs transplantation. After hUC-MSCs transplantation, the prothrombin time was lower than before. The levels of hyaluronic acid and IV-C(Type IV collagen) in fibrotic indicators were significantly reduced, and the Young's modulus was also decreased. Moreover, liver biopsy showed that the lytic necrosis of hepatocyte was decreased. In liver hemodynamics, the portal vein diameter was decreased after hUC-MSCs transplantation. hUC-MSCs transplantation can alleviate liver damage caused by LC. The improved "retentional metal stiffner trocar" of pig-tail catheter was safe and effective in the infusion of hUC-MSCs transplantation, which is worth promoting in clinical practice.

Repeated human cranial bone-derived mesenchymal stem cell transplantation improved electrophysiological recovery in a spinal cord injury rat model

Mesenchymal stem cell (MSC)-based therapy has been applied in several clinical trials of spinal cord injury (SCI). We have successfully established MSCs from human cranial bone and developed a longitudinal neuromonitoring technique for rodents. In addition to single transplantation, the potential of multiple transplantations has been suggested as a new therapeutic strategy. However, there are no reports on the electrophysiological effects of multiple MSC transplantations in SCI using transcranial electrical stimulation motor-evoked potentials (tcMEPs). Here, we aimed to elucidate the efficacy and mechanism of action of multiple MSC transplantations using tcMEPs. After establishing a weight-drop-induced SCI rat model, we performed repeated intravenous transplantation of human cranial bone-derived MSCs (hcMSCs) on days 1 and 3 post-SCI. Motor function and tcMEP recovery were evaluated 6weeks post-transplantation. Tissue repair post-SCI was assessed using immunostaining for myelin and neurons in the injured posterior cord. Repeated hcMSC transplantation significantly improved motor function and electrophysiological recovery compared to single transplantation and control treatment. Repeated hcMSC transplantation promoted electrophysiological functional recovery by exerting a protective effect on the functional structure of pyramidal tract axons. Thus, acute-phase repeated transplantation could be a novel and effective therapeutic strategy for the clinical application of MSCs in SCI.

Hypoxia-Preconditioned Human Umbilical Cord Mesenchymal Stem Cells Transplantation Ameliorates Inflammation and Bone Regeneration in Peri-Implantitis Rat Model.

The failure of dental implant treatments is predominantly attributed to peri-implantitis, which entails chronic inflammation within the peri-implant tissue, ultimately leading to tissue degradation. Addressing this condition, human umbilical cord mesenchymal stem cell (hUCMSC) transplantation serves as a regenerative therapy; however, concerns regarding the viability and efficacy of transplanted cells in inflamed regions persist. Hypoxic preconditioning of hUCMSCs has emerged as a potential strategy for augmenting their regenerative and immunomodulatory capacities. This study aimed to evaluate the expression of inflammatory (tumor necrosis factor [TNF]-α) and bone regenerative biomarkers (nuclear factor of activated T-cell [NFATc1], osteocalcin, collagen type I alpha 1 [COL1α1]) within peri-implantitis models subsequent to the transplantation of hypoxia-preconditioned hUCMSCs. Peri-implantitis models were established through the insertion of implants into the femur bone of 42 Wistar strain Rattus norvegicus, followed by intrasocket injection of lipopolysaccharide. The experimental animals were categorized into three groups (control, normoxia, and hypoxia) and underwent observation on days 14 and 28. The expression levels of TNF-α, NFATc1, COL1α1, and osteocalcin were evaluated using immunohistochemical staining, and the resulting data were subjected to one-way analysis of variance analysis (p < 0.05). Transplantation of hypoxia-preconditioned hUCMSCs significantly ameliorated inflammation and osteoclastogenesis, as evidenced by significant reductions in TNF-α and NFATc1 expression compared with the control group. Furthermore, hypoxic preconditioning of hUCMSCs demonstrated a significant elevation in the expression of osteocalcin and COL1α1 relative to the control group. The transplantation of hypoxia-preconditioned hUCMSCs exhibited a capacity to ameliorate inflammation and enhance bone regenerative processes in peri-implantitis rat models.

Stem cell transplantation extends the reproductive life span of naturally aging cynomolgus monkeys

The ovary is crucial for female reproduction and health, as it generates oocytes and secretes sex hormones. Transplantation of mesenchymal stem cells (MSCs) has been shown to alleviate pathological ovarian aging. However, it is unclear whether MSCs could benefit the naturally aging ovary. In this study, we first examined the dynamics of ovarian reserve of Chinese women during perimenopause. Using a naturally aging cynomolgus monkey (Macaca fascicularis) model, we found that transplanting human embryonic stem cells-derived MSC-like cells, which we called M cells, into the aging ovaries significantly decreased ovarian fibrosis and DNA damage, enhanced secretion of sex hormones and improved fertility. Encouragingly, a healthy baby monkey was born after M-cell transplantation. Moreover, single-cell RNA sequencing analysis and in vitro functional validation suggested that apoptosis, oxidative damage, inflammation, and fibrosis were mitigated in granulosa cells and stromal cells following M-cell transplantation. Altogether, these findings demonstrate the beneficial effects of M-cell transplantation on aging ovaries and expand our understanding of the molecular mechanisms underlying ovarian aging and stem cell-based alleviation of this process.

Suprachoroidal Umbilical Cord-Derived Mesenchymal Stem Cell Transplantation for the Regeneration of Glaucomatous Optic Neuropathy: A Preliminary Investigation

Objective: This preliminary research presents clinical findings from patients with advanced Glaucomatous Optic Neuropathy (GON) who underwent transplantation of Umbilical Cord-Derived Mesenchymal Stem Cells (UCMSCs) into the suprachoroidal space. Methods: This prospective, single-center study included 17 eyes of 17 patients diagnosed with GON, who received suprachoroidal UCMSC implantation. Patients were registered if their visual acuity and/or Visual Field (VF) deteriorated despite maintaining good intraocular pressure control with anti-glaucomatous treatments. Evaluations were conducted at baseline, on the first postoperative day and at 1 month, 6 months and 1 year after surgery. Best Corrected Visual Acuity (BCVA), anterior segment and fundus examination, color photography, Optical Coherence Tomography (OCT), Retinal Nerve Fiber Layer (RNFL) analysis, VF testing and Pattern Visual Evoked Potential (PVEP) assessments were performed at baseline and during follow-up visits. Results: All 17 participants completed the 12-month follow-up period. No systemic or serious ocular complications were recorded. The study showed significant improvements in BCVA, VF results, RNFL measurements and PVEP amplitudes at the end of the follow-up period. Conclusion: Although the sample size is limited, suprachoroidal UCMSC therapy appears to be safe, with encouraging improvements. Further studies with larger patient groups and longer follow-up periods are required to assess the impact of stem cell delivery on visual acuity and quality of life in glaucoma patients.

Intravenous transplantation of autologous adipose-derived mesenchymal stem cells for chronic stage ischemic stroke: a case report of rapid and dramatic improvement and review of the literature

Intravenous transplantation of autologous adipose-derived mesenchymal stem cells for chronic stage ischemic stroke: a case report of rapid and dramatic improvement and review of the literature

Overview of emerging therapies for demyelinating diseases.

This paper provides an overview of autoimmune disorders of the central nervous system, specifically those caused by demyelination. We explore new research regarding potential therapeutic interventions, particularly those aimed at inducing remyelination. Remyelination is a detailed process, involving many cell types-oligodendrocyte precursor cells (OPCs), astrocytes, and microglia-and both the innate and adaptive immune systems. Our discussion of this process includes the differentiation potential of neural stem cells, the function of adult OPCs, and the impact of molecular mediators on myelin repair. Emerging therapies are also explored, with mechanisms of action including the induction of OPC differentiation, the transplantation of mesenchymal stem cells, and the use of molecular mediators. Further, we discuss current medical advancements in relation to many myelin-related disorders, including multiple sclerosis, optic neuritis, neuromyelitis optica spectrum disorder, myelin oligodendrocyte glycoprotein antibody-associated disease, transverse myelitis, and acute disseminated encephalomyelitis. Beyond these emerging systemic therapies, we also introduce the dimethyl fumarate/silk fibroin nerve conduit and its potential role in the treatment of peripheral nerve injuries. Despite these aforementioned scientific advancements, this paper maintains the need for ongoing research to deepen our understanding of demyelinating diseases and advance therapeutic strategies that enhance affected patients' quality of life.

Mesenchymal stem cell transplant as an intervention to ameliorate disuse-induced muscle atrophy in a mouse model of simulated microgravity

Mesenchymal stem cell transplant as an intervention to ameliorate disuse-induced muscle atrophy in a mouse model of simulated microgravity

Transplantation of human umbilical cord-derived mesenchymal stem cells improves age-related ovarian functional decline via regulating the local renin–angiotensin system on inflammation and oxidative stress

BackgroundAge-related reproductive aging is a natural and irreversible physiological process, and delaying childbearing is increasingly common all over the world. Transplantation of mesenchymal stem cells (MSCs) is considered a new and effective therapy to restore ovarian function, but the relevant mechanisms remain unclear. Recently, it has been found that there is a local Renin–angiotensin system (RAS) in human ovary and it plays a key role.MethodsAfter collecting follicular fluid from women who received oocyte retrieval for pure male factor infertility, the level of RAS components in it were detected, and the correlation analysis by linear regression. Then, the in vivo experiments on female C57BL/6 mice were designed to measure ovarian function, and the transcription and translation levels of RAS pathway were detected by molecular biology methods. Moreover, the role of RAS in regulating inflammation and oxidative stress in the co-culture system were explored in in vitro experiments on KGN cells.ResultsFirst, a total of 139 samples of analyzable follicular fluid were obtained. The local RAS of ovary, which is independent of systemic RAS (P > 0.05), is affected by age (Pearson r < 0, P < 0.05) and related to ovarian function, inflammation, oxidative stress indexes and assisted reproduction laboratory outcomes (P < 0.05). Next, the ovary/body weight of aging mice decreased significantly and serum sex hormones levels changed significantly (P < 0.01). The number of functional follicles decreased, while the atresia follicles increased (P < 0.05). After MSCs transplantation, all the above measures have been partially recovered (P < 0.05). Although several RAS components in aging ovary changed, MSCs only improved the expression level of AT1R (P < 0.05). Furthermore, the secretion ability and mitochondrial membrane potential of aging KGN cells decreased, while the intracellular ROS level and the aging cells ratio increased (P < 0.01). All the above measures have been partially recovered when co-cultured with MSCs (P < 0.05). After Ang(1–7) were added into the co-culture system, the above have been more significantly restored compared with Ang II (P < 0.05). Nevertheless, there was no statistical difference in estradiol level no matter which one was added (P > 0.05).ConclusionsTogether, our findings indicate that a novel possible mechanism to explain how stem cells restore age-related ovarian functional decline.