Currently, there is no effective strategy to promote functional recovery after a spinal cord injury. Collagen scaffolds can not only provide support and guidance for axonal regeneration, but can also serve as a bridge...Currently, there is no effective strategy to promote functional recovery after a spinal cord injury. Collagen scaffolds can not only provide support and guidance for axonal regeneration, but can also serve as a bridge for nerve regeneration at the injury site. They can additionally be used as carriers to retain mesenchymal stem cells at the injury site to enhance their effectiveness. Hence, we hypothesized that transplanting human umbilical cord-mesenchymal stem cells on collagen scaffolds would enhance healing following acute complete spinal cord injury. Here, we test this hypothesis through animal studies and a phase I clinical trial.(1) Animal experiments: Models of completely transected spinal cord injury were established in rats and canines by microsurgery. Mesenchymal stem cells derived from neonatal umbilical cord tissue were adsorbed onto collagen scaffolds and surgically implanted at the injury site in rats and canines;the animals were observed after 1 week–6 months. The transplantation resulted in increased motor scores, enhanced amplitude and shortened latency of the motor evoked potential, and reduced injury area as measured by magnetic resonance imaging.(2) Phase I clinical trial: Forty patients with acute complete cervical injuries were enrolled at the Characteristic Medical Center of Chinese People's Armed Police Force and divided into two groups. The treatment group(n = 20) received collagen scaffolds loaded with mesenchymal stem cells derived from neonatal umbilical cordtissues;the control group(n = 20) did not receive the stem-cell loaded collagen implant. All patients were followed for 12 months. In the treatment group, the American Spinal Injury Association scores and activities of daily life scores were increased, bowel and urinary functions were recovered, and residual urine volume was reduced compared with the pre-treatment baseline. Furthermore, magnetic resonance imaging showed that new nerve fiber connections were formed, and diffusion tensor imaging showed that electrophysiological ac展开更多
Studies on ischemia/reperfusion(I/R)injury suggest that exogenous neural stem cells(NSCs)are ideal candidates for stem cell therapy reperfusion injury.However,NSCs are difficult to obtain owing to ethical limitations....Studies on ischemia/reperfusion(I/R)injury suggest that exogenous neural stem cells(NSCs)are ideal candidates for stem cell therapy reperfusion injury.However,NSCs are difficult to obtain owing to ethical limitations.In addition,the survival,differentiation,and proliferation rates of transplanted exogenous NSCs are low,which limit their clinical application.Our previous study showed that neuregulin1β(NRG1β)alleviated cerebral I/R injury in rats.In this study,we aimed to induce human umbilical cord mesenchymal stem cells into NSCs and investigate the improvement effect and mechanism of NSCs pretreated with 10 nM NRG1βon PC12 cells injured by oxygen-glucose deprivation/reoxygenation(OGD/R).Our results found that 5 and 10 nM NRG1βpromoted the generation and proliferation of NSCs.Co-culture of NSCs and PC12 cells under condition of OGD/R showed that pretreatment of NSCs with NRG1βimproved the level of reactive oxygen species,malondialdehyde,glutathione,superoxide dismutase,nicotinamide adenine dinucleotide phosphate,and nuclear factor erythroid 2-related factor 2(Nrf2)and mitochondrial damage in injured PC12 cells;these indexes are related to ferroptosis.Research has reported that p53 and solute carrier family 7 member 11(SLC7A11)play vital roles in ferroptosis caused by cerebral I/R injury.Our data show that the expression of p53 was increased and the level of glutathione peroxidase 4(GPX4)was decreased after RNA interference-mediated knockdown of SLC7A11 in PC12 cells,but this change was alleviated after co-culturing NSCs with damaged PC12 cells.These findings suggest that NSCs pretreated with NRG1βexhibited neuroprotective effects on PC12 cells subjected to OGD/R through influencing the level of ferroptosis regulated by p53/SLC7A11/GPX4 pathway.展开更多
BACKGROUND Progressive pancreaticβcell dysfunction is a fundamental aspect of the pathology underlying type 2 diabetes mellitus(T2DM).Recently,mesenchymal stem cell(MSC)transplantation has emerged as a new therapeuti...BACKGROUND Progressive pancreaticβcell dysfunction is a fundamental aspect of the pathology underlying type 2 diabetes mellitus(T2DM).Recently,mesenchymal stem cell(MSC)transplantation has emerged as a new therapeutic method due to its ability to promote the regeneration of pancreaticβcells.However,current studies have focused on its efficacy,and there are few clinical studies on its safety.AIM To evaluate the safety of human umbilical cord(hUC)-MSC infusion in T2DM treatment.METHODS An open-label and randomized phase 2 clinical trial was designed to evaluate the safety of hUC-MSC transplantation in T2DM in a Class A hospital.Ten patients in the placebo group received acellular saline intravenously once per week for 3 wk.Twenty-four patients in the hUC-MSC group received hUC-MSCs(1×106 cells/kg)intravenously once per week for 3 wk.Diabetic clinical symptoms and signs,laboratory findings,and imaging findings were evaluated weekly for the 1st mo and then at weeks 12 and 24 post-treatment.RESULTS No serious adverse events were observed during the 24-wk follow-up.Four patients(16.7%)in the hUC-MSC group experienced transient fever,which occurred within 24 h after the second or third infusion;this did not occur in any patients in the placebo group.One patient from the hUC-MSC group experienced hypoglycemic attacks within 1 mo after transplantation.Significantly lower lymphocyte levels(weeks 2 and 3)and thrombin coagulation time(week 2)were observed in the hUC-MSC group compared to those in the placebo group(all P<0.05).Significantly higher platelet levels(week 3),immunoglobulin levels(weeks 1,2,3,and 4),fibrinogen levels(weeks 2 and 3),D-dimer levels(weeks 1,2,3,4,12,and 24),and neutrophil-to-lymphocyte ratios(weeks 2 and 3)were observed in the hUC-MSC group compared to those in the placebo group(all P<0.05).There were no significant differences between the two groups for tumor markers(alpha-fetoprotein,carcinoembryonic antigen,and carbohydrate antigen 199)or blood fat.No liver damage or other side effects were obs展开更多
BACKGROUND Bell’s palsy is an idiopathic facial palsy with an unknown cause,and 75%of patients heal spontaneously.However,the other 25%of patients continue experiencing mild or severe disabilities,resulting in a redu...BACKGROUND Bell’s palsy is an idiopathic facial palsy with an unknown cause,and 75%of patients heal spontaneously.However,the other 25%of patients continue experiencing mild or severe disabilities,resulting in a reduced quality of life.Currently,various treatment methods have been developed to treat this disease.However,there is controversy regarding their effectiveness,and new alternative treatments are needed.CASE SUMMARY The patient suffered from left-sided facial paralysis due to Bell’s palsy for 7 years.The patient received an uncultured umbilical cord-derived mesenchymal stem cell transplant eight times for treatment.After follow-up for 32 mo,the paralysis was cured,and there was no recurrence.CONCLUSION Uncultured umbilical cord-derived mesenchymal stem cell transplantation may be a potential treatment for patients with Bell’s palsy who do not spontaneously recover.展开更多
BACKGROUND Heart diseases are the primary cause of death all over the world.Following myocardial infarction,billions of cells die,resulting in a huge loss of cardiac function.Stem cell-based therapies have appeared as...BACKGROUND Heart diseases are the primary cause of death all over the world.Following myocardial infarction,billions of cells die,resulting in a huge loss of cardiac function.Stem cell-based therapies have appeared as a new area to support heart regeneration.The transcription factors GATA binding protein 4(GATA-4)and myocyte enhancer factor 2C(MEF2C)are considered prominent factors in the development of the cardiovascular system.AIM To explore the potential of GATA-4 and MEF2C for the cardiac differentiation of human umbilical cord mesenchymal stem cells(hUC-MSCs).METHODS hUC-MSCs were characterized morphologically and immunologically by the presence of specific markers of MSCs via immunocytochemistry and flow cytometry,and by their potential to differentiate into osteocytes and adipocytes.hUC-MSCs were transfected with GATA-4,MEF2C,and their combination to direct the differentiation.Cardiac differentiation was confirmed by semiquant itative real-time polymerase chain reaction and immunocytochemistry.RESULTS hUC-MSCs expressed specific cell surface markers CD105,CD90,CD44,and vimentin but lack the expression of CD45.The transcription factors GATA-4 and MEF2C,and their combination induced differentiation in hUC-MSCs with significant expression of cardiac genes i.e.,GATA-4,MEF2C,NK2 homeobox 5(NKX2.5),MHC,and connexin-43,and cardiac proteins GATA-4,NKX2.5,cardiac troponin T,and connexin-43.CONCLUSION Transfection with GATA-4,MEF2C,and their combination effectively induces cardiac differentiation in hUC-MSCs.These genetically modified MSCs could be a promising treatment option for heart diseases in the future.展开更多
With technological advances in basic research,the intricate mechanism of secondary delayed spinal cord injury(SCI)continues to unravel at a rapid pace.However,despite our deeper understanding of the molecular changes ...With technological advances in basic research,the intricate mechanism of secondary delayed spinal cord injury(SCI)continues to unravel at a rapid pace.However,despite our deeper understanding of the molecular changes occurring after initial insult to the spinal cord,the cure for paralysis remains elusive.Current treatment of SCI is limited to early administration of high dose steroids to mitigate the harmful effect of cord edema that occurs after SCI and to reduce the cascade of secondary delayed SCI.R ecent evident-based clinical studies have cast doubt on the clinical benefit of steroids in SCI and intense focus on stem cell-based therapy has yielded some encouraging results.An array of mesenchymal stem cells(MSCs)from various sources with novel and promising strategies are being developed to improve function after SCI.In this review,we briefly discuss the pathophysiology of spinal cord injuries and characteristics and the potential sources of MSCs that can be used in the treatment of SCI.We will discuss the progress of MSCs application in research,focusing on the neuroprotective properties of MSCs.Finally,we will discuss the results from preclinical and clinical trials involving stem cell-based therapy in SCI.展开更多
Objective:To observe the effect of Rougan Huaqian granules combined with human mesenchymal stem cell(hMSC)transplantation on the liver fibrosis in carbon tetrachlorideinduced cirrhosis rats.Methods:Sixty SD rats were ...Objective:To observe the effect of Rougan Huaqian granules combined with human mesenchymal stem cell(hMSC)transplantation on the liver fibrosis in carbon tetrachlorideinduced cirrhosis rats.Methods:Sixty SD rats were randomly divided into live groups.The rats in control group received intraperitoneal injection of saline,while those in model control group,treatment group A,group B and group C received intraperitoneal injection of carbon tetrachloride oily solution to induce liver cirrhosis within 8 weeks.Then,the rats in the model control group,treatment group A,treatment group B,treatment group C received vein tail injection of saline,Rougan Huaqian granules,hMSC suspension and Rougan Huaqian granules combined with hMSC suspension.Results:The treatment groups had significantly different liver function(AST levels),liver fibrosis index(laminin and HA),hepatic sinusoidal wallsα-smooth muscle actin,Ⅳcollagen and laminin protein expression andⅠ,Ⅲcollagen from the model group(P<0.05).The transplanted cells showed human hepatocyte-like cells differentiation trend in the liver.Conclusions:The Rougan Huaqian granules combined with hMSC transplantation can alleviate liver fibrosis in cirrhosis rats.展开更多
基金supported by the National Natural Science Foundation of China,Nos.11932013(to SZ),11672332(to SZ)the National Key Research and Development Plan of China,No.2016YFC1101500(to SZ)+2 种基金the Science and Technology Military-Civilian Integration Project of Tianjin of China,No.18ZXJMTG00260(to XYC)the Key Project of Science and Technology Support Plan of Tianjin of China,No.17YFZCSY00620(to XYC)the Rescue Medical Clinical Center Fund of Tianjin of China,No.15ZXLCSY00040(to XYC)
文摘Currently, there is no effective strategy to promote functional recovery after a spinal cord injury. Collagen scaffolds can not only provide support and guidance for axonal regeneration, but can also serve as a bridge for nerve regeneration at the injury site. They can additionally be used as carriers to retain mesenchymal stem cells at the injury site to enhance their effectiveness. Hence, we hypothesized that transplanting human umbilical cord-mesenchymal stem cells on collagen scaffolds would enhance healing following acute complete spinal cord injury. Here, we test this hypothesis through animal studies and a phase I clinical trial.(1) Animal experiments: Models of completely transected spinal cord injury were established in rats and canines by microsurgery. Mesenchymal stem cells derived from neonatal umbilical cord tissue were adsorbed onto collagen scaffolds and surgically implanted at the injury site in rats and canines;the animals were observed after 1 week–6 months. The transplantation resulted in increased motor scores, enhanced amplitude and shortened latency of the motor evoked potential, and reduced injury area as measured by magnetic resonance imaging.(2) Phase I clinical trial: Forty patients with acute complete cervical injuries were enrolled at the Characteristic Medical Center of Chinese People's Armed Police Force and divided into two groups. The treatment group(n = 20) received collagen scaffolds loaded with mesenchymal stem cells derived from neonatal umbilical cordtissues;the control group(n = 20) did not receive the stem-cell loaded collagen implant. All patients were followed for 12 months. In the treatment group, the American Spinal Injury Association scores and activities of daily life scores were increased, bowel and urinary functions were recovered, and residual urine volume was reduced compared with the pre-treatment baseline. Furthermore, magnetic resonance imaging showed that new nerve fiber connections were formed, and diffusion tensor imaging showed that electrophysiological ac
基金supported by the National Natural Science Foundation of China,No.81973501the Natural Science Foundation of Shandong Province,No.ZR2019MH009(both to YLG).
文摘Studies on ischemia/reperfusion(I/R)injury suggest that exogenous neural stem cells(NSCs)are ideal candidates for stem cell therapy reperfusion injury.However,NSCs are difficult to obtain owing to ethical limitations.In addition,the survival,differentiation,and proliferation rates of transplanted exogenous NSCs are low,which limit their clinical application.Our previous study showed that neuregulin1β(NRG1β)alleviated cerebral I/R injury in rats.In this study,we aimed to induce human umbilical cord mesenchymal stem cells into NSCs and investigate the improvement effect and mechanism of NSCs pretreated with 10 nM NRG1βon PC12 cells injured by oxygen-glucose deprivation/reoxygenation(OGD/R).Our results found that 5 and 10 nM NRG1βpromoted the generation and proliferation of NSCs.Co-culture of NSCs and PC12 cells under condition of OGD/R showed that pretreatment of NSCs with NRG1βimproved the level of reactive oxygen species,malondialdehyde,glutathione,superoxide dismutase,nicotinamide adenine dinucleotide phosphate,and nuclear factor erythroid 2-related factor 2(Nrf2)and mitochondrial damage in injured PC12 cells;these indexes are related to ferroptosis.Research has reported that p53 and solute carrier family 7 member 11(SLC7A11)play vital roles in ferroptosis caused by cerebral I/R injury.Our data show that the expression of p53 was increased and the level of glutathione peroxidase 4(GPX4)was decreased after RNA interference-mediated knockdown of SLC7A11 in PC12 cells,but this change was alleviated after co-culturing NSCs with damaged PC12 cells.These findings suggest that NSCs pretreated with NRG1βexhibited neuroprotective effects on PC12 cells subjected to OGD/R through influencing the level of ferroptosis regulated by p53/SLC7A11/GPX4 pathway.
基金Shenzhen Science and Technology Innovation Committee Projects,No.JCYJ20170816105416349Shenzhen High-Level Hospital Construction Fund,Shenzhen Key Medical Discipline Construction Fund,No.SZXK010.
文摘BACKGROUND Progressive pancreaticβcell dysfunction is a fundamental aspect of the pathology underlying type 2 diabetes mellitus(T2DM).Recently,mesenchymal stem cell(MSC)transplantation has emerged as a new therapeutic method due to its ability to promote the regeneration of pancreaticβcells.However,current studies have focused on its efficacy,and there are few clinical studies on its safety.AIM To evaluate the safety of human umbilical cord(hUC)-MSC infusion in T2DM treatment.METHODS An open-label and randomized phase 2 clinical trial was designed to evaluate the safety of hUC-MSC transplantation in T2DM in a Class A hospital.Ten patients in the placebo group received acellular saline intravenously once per week for 3 wk.Twenty-four patients in the hUC-MSC group received hUC-MSCs(1×106 cells/kg)intravenously once per week for 3 wk.Diabetic clinical symptoms and signs,laboratory findings,and imaging findings were evaluated weekly for the 1st mo and then at weeks 12 and 24 post-treatment.RESULTS No serious adverse events were observed during the 24-wk follow-up.Four patients(16.7%)in the hUC-MSC group experienced transient fever,which occurred within 24 h after the second or third infusion;this did not occur in any patients in the placebo group.One patient from the hUC-MSC group experienced hypoglycemic attacks within 1 mo after transplantation.Significantly lower lymphocyte levels(weeks 2 and 3)and thrombin coagulation time(week 2)were observed in the hUC-MSC group compared to those in the placebo group(all P<0.05).Significantly higher platelet levels(week 3),immunoglobulin levels(weeks 1,2,3,and 4),fibrinogen levels(weeks 2 and 3),D-dimer levels(weeks 1,2,3,4,12,and 24),and neutrophil-to-lymphocyte ratios(weeks 2 and 3)were observed in the hUC-MSC group compared to those in the placebo group(all P<0.05).There were no significant differences between the two groups for tumor markers(alpha-fetoprotein,carcinoembryonic antigen,and carbohydrate antigen 199)or blood fat.No liver damage or other side effects were obs
文摘BACKGROUND Bell’s palsy is an idiopathic facial palsy with an unknown cause,and 75%of patients heal spontaneously.However,the other 25%of patients continue experiencing mild or severe disabilities,resulting in a reduced quality of life.Currently,various treatment methods have been developed to treat this disease.However,there is controversy regarding their effectiveness,and new alternative treatments are needed.CASE SUMMARY The patient suffered from left-sided facial paralysis due to Bell’s palsy for 7 years.The patient received an uncultured umbilical cord-derived mesenchymal stem cell transplant eight times for treatment.After follow-up for 32 mo,the paralysis was cured,and there was no recurrence.CONCLUSION Uncultured umbilical cord-derived mesenchymal stem cell transplantation may be a potential treatment for patients with Bell’s palsy who do not spontaneously recover.
基金Supported by the Higher Education Commission(HEC),Pakistan Scholarship for Ph.D.Studies to Razzaq SS,No.520-148390-2BS6-011.
文摘BACKGROUND Heart diseases are the primary cause of death all over the world.Following myocardial infarction,billions of cells die,resulting in a huge loss of cardiac function.Stem cell-based therapies have appeared as a new area to support heart regeneration.The transcription factors GATA binding protein 4(GATA-4)and myocyte enhancer factor 2C(MEF2C)are considered prominent factors in the development of the cardiovascular system.AIM To explore the potential of GATA-4 and MEF2C for the cardiac differentiation of human umbilical cord mesenchymal stem cells(hUC-MSCs).METHODS hUC-MSCs were characterized morphologically and immunologically by the presence of specific markers of MSCs via immunocytochemistry and flow cytometry,and by their potential to differentiate into osteocytes and adipocytes.hUC-MSCs were transfected with GATA-4,MEF2C,and their combination to direct the differentiation.Cardiac differentiation was confirmed by semiquant itative real-time polymerase chain reaction and immunocytochemistry.RESULTS hUC-MSCs expressed specific cell surface markers CD105,CD90,CD44,and vimentin but lack the expression of CD45.The transcription factors GATA-4 and MEF2C,and their combination induced differentiation in hUC-MSCs with significant expression of cardiac genes i.e.,GATA-4,MEF2C,NK2 homeobox 5(NKX2.5),MHC,and connexin-43,and cardiac proteins GATA-4,NKX2.5,cardiac troponin T,and connexin-43.CONCLUSION Transfection with GATA-4,MEF2C,and their combination effectively induces cardiac differentiation in hUC-MSCs.These genetically modified MSCs could be a promising treatment option for heart diseases in the future.
基金Supported by A grant from Illinois Neurological Institute to DHD
文摘With technological advances in basic research,the intricate mechanism of secondary delayed spinal cord injury(SCI)continues to unravel at a rapid pace.However,despite our deeper understanding of the molecular changes occurring after initial insult to the spinal cord,the cure for paralysis remains elusive.Current treatment of SCI is limited to early administration of high dose steroids to mitigate the harmful effect of cord edema that occurs after SCI and to reduce the cascade of secondary delayed SCI.R ecent evident-based clinical studies have cast doubt on the clinical benefit of steroids in SCI and intense focus on stem cell-based therapy has yielded some encouraging results.An array of mesenchymal stem cells(MSCs)from various sources with novel and promising strategies are being developed to improve function after SCI.In this review,we briefly discuss the pathophysiology of spinal cord injuries and characteristics and the potential sources of MSCs that can be used in the treatment of SCI.We will discuss the progress of MSCs application in research,focusing on the neuroprotective properties of MSCs.Finally,we will discuss the results from preclinical and clinical trials involving stem cell-based therapy in SCI.
基金supported by the Guangxi Scientific and Technological Project(No.11107009-3-1)Guangxi Natural Science Fund Projects(No.2010 GXNSFA013211)
文摘Objective:To observe the effect of Rougan Huaqian granules combined with human mesenchymal stem cell(hMSC)transplantation on the liver fibrosis in carbon tetrachlorideinduced cirrhosis rats.Methods:Sixty SD rats were randomly divided into live groups.The rats in control group received intraperitoneal injection of saline,while those in model control group,treatment group A,group B and group C received intraperitoneal injection of carbon tetrachloride oily solution to induce liver cirrhosis within 8 weeks.Then,the rats in the model control group,treatment group A,treatment group B,treatment group C received vein tail injection of saline,Rougan Huaqian granules,hMSC suspension and Rougan Huaqian granules combined with hMSC suspension.Results:The treatment groups had significantly different liver function(AST levels),liver fibrosis index(laminin and HA),hepatic sinusoidal wallsα-smooth muscle actin,Ⅳcollagen and laminin protein expression andⅠ,Ⅲcollagen from the model group(P<0.05).The transplanted cells showed human hepatocyte-like cells differentiation trend in the liver.Conclusions:The Rougan Huaqian granules combined with hMSC transplantation can alleviate liver fibrosis in cirrhosis rats.
