Objective To investigate a possibility of repairing damaged brain by intracerebroventricular transplantation of neural stem cells （NSCs） in the adult mice subjected to glutamate-induced excitotoxic injury. Methods M...Objective To investigate a possibility of repairing damaged brain by intracerebroventricular transplantation of neural stem cells （NSCs） in the adult mice subjected to glutamate-induced excitotoxic injury. Methods Mouse NSCs were isolated from the brains of embryos at 15-day postcoitum （dpc）. The expression of nestin, a special antigen for NSC, was detected by immunocytochemistry. Immunofluorescence staining was carried out to observe the survival and location of transplanted NSCs. The animals in the MSG＋NSCs group received intracerebroventricular transplantation of NSCs （approximately 1.0×10^5 cells） separately on day 1 and day 10 after 10-d MSG exposure （4.0 g/kg per day）. The mice in control and MSG groups received intracerebroventricular injection of Dulbecco＇s minimum essential medium （DMEM） instead of NSCs. On day 11 after the last NSC transplantation, the test of Y-maze discrimination learning was performed, and then the histopathology of the animal brains was studied to analyze the MSG-induced functional and morphological changes of brain and the effects of intracerebroventricular transplantation of NSCs on the brain repair. Results The isolated cells were Nestin-positive. The grafted NSCs in the host brain were region-specifically survived at 10-d post-transplantation. Intracerebroventricular transplantation of NSCs obviously facilitated the brain recovery from glutamate-induced behavioral disturbances and histopathological impairs in adult mice. Conclusion Intracerebroventricular transplantation of NSCs may be feasible in repairing diseased or damaged brain tissue.展开更多
Multiple sclerosis(MS) is an autoimmune disease of the central nervous system(CNS), with focal T lymphocytic infiltration and damage of myelin and axons. The underlying mechanism of pathogenesis remains unclear and th...Multiple sclerosis(MS) is an autoimmune disease of the central nervous system(CNS), with focal T lymphocytic infiltration and damage of myelin and axons. The underlying mechanism of pathogenesis remains unclear and there are currently no effective treatments. The development of neural stem cell(NSC) transplantation provides a promising strategy to treat neurodegenerative disease. However, the limited availability of NSCs prevents their application in neural disease therapy. In this study, we generated NSCs from induced pluripotent stem cells(iPSCs) and transplanted these cells into mice with experimental autoimmune encephalomyelitis(EAE), a model of MS. The results showed that transplantation of iPSC-derived NSCs dramatically reduced T cell infiltration and ameliorated white matter damage in the treated EAE mice. Correspondingly, the disease symptom score was greatly decreased, and motor ability was dramatically rescued in the iPSC-NSC-treated EAE mice, indicating the effectiveness of using iPSC-NSCs to treat MS. Our study provides pre-clinical evidence to support the feasibility of treating MS by transplantation of iPSC-derived NSCs.展开更多
Objective: To explore the culture conditions of human neural stem cells and to investigate the ultrastructure of neurospheres. Methods: The cells from the embryonic human cortices were mechanically dissociated. N2 med...Objective: To explore the culture conditions of human neural stem cells and to investigate the ultrastructure of neurospheres. Methods: The cells from the embryonic human cortices were mechanically dissociated. N2 medium was adapted to culture and expand the cells. The cells were identified by immunocytochemistry and EM was applied to examine the ultrastructure of neurospheres. Results: The neural stem cells from human embryonic brains were successfully cultured and formed typical neurospheres in suspension, and most of the cells expressed vimentin, which was a marker for neural progenitor cells, and the cells could differentiate into neurons, astrocytes and oligodendrocytes. In vitro myelin formation in neurospheres were observed at an early stage of culture. Conclusions: Human neural stem cells can be cultured from embryonic brains, can form the typical neurospheres in suspension in vitro and have the ability of myelinating, and may be potential source for transplantation in treating myelin disorders.展开更多
文摘Objective To investigate a possibility of repairing damaged brain by intracerebroventricular transplantation of neural stem cells （NSCs） in the adult mice subjected to glutamate-induced excitotoxic injury. Methods Mouse NSCs were isolated from the brains of embryos at 15-day postcoitum （dpc）. The expression of nestin, a special antigen for NSC, was detected by immunocytochemistry. Immunofluorescence staining was carried out to observe the survival and location of transplanted NSCs. The animals in the MSG＋NSCs group received intracerebroventricular transplantation of NSCs （approximately 1.0×10^5 cells） separately on day 1 and day 10 after 10-d MSG exposure （4.0 g/kg per day）. The mice in control and MSG groups received intracerebroventricular injection of Dulbecco＇s minimum essential medium （DMEM） instead of NSCs. On day 11 after the last NSC transplantation, the test of Y-maze discrimination learning was performed, and then the histopathology of the animal brains was studied to analyze the MSG-induced functional and morphological changes of brain and the effects of intracerebroventricular transplantation of NSCs on the brain repair. Results The isolated cells were Nestin-positive. The grafted NSCs in the host brain were region-specifically survived at 10-d post-transplantation. Intracerebroventricular transplantation of NSCs obviously facilitated the brain recovery from glutamate-induced behavioral disturbances and histopathological impairs in adult mice. Conclusion Intracerebroventricular transplantation of NSCs may be feasible in repairing diseased or damaged brain tissue.
基金supported by the China National Basic Research Program(2013CB966901,2012CBA01303)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA01040108)+1 种基金National Thousand Young Talents Program to Tongbiao Zhaothe National Natural Science Foundation of China Program((31271592,31570995)to Tongbiao Zhao,(31400831)to Jiani Cao)
文摘Multiple sclerosis(MS) is an autoimmune disease of the central nervous system(CNS), with focal T lymphocytic infiltration and damage of myelin and axons. The underlying mechanism of pathogenesis remains unclear and there are currently no effective treatments. The development of neural stem cell(NSC) transplantation provides a promising strategy to treat neurodegenerative disease. However, the limited availability of NSCs prevents their application in neural disease therapy. In this study, we generated NSCs from induced pluripotent stem cells(iPSCs) and transplanted these cells into mice with experimental autoimmune encephalomyelitis(EAE), a model of MS. The results showed that transplantation of iPSC-derived NSCs dramatically reduced T cell infiltration and ameliorated white matter damage in the treated EAE mice. Correspondingly, the disease symptom score was greatly decreased, and motor ability was dramatically rescued in the iPSC-NSC-treated EAE mice, indicating the effectiveness of using iPSC-NSCs to treat MS. Our study provides pre-clinical evidence to support the feasibility of treating MS by transplantation of iPSC-derived NSCs.
文摘Objective: To explore the culture conditions of human neural stem cells and to investigate the ultrastructure of neurospheres. Methods: The cells from the embryonic human cortices were mechanically dissociated. N2 medium was adapted to culture and expand the cells. The cells were identified by immunocytochemistry and EM was applied to examine the ultrastructure of neurospheres. Results: The neural stem cells from human embryonic brains were successfully cultured and formed typical neurospheres in suspension, and most of the cells expressed vimentin, which was a marker for neural progenitor cells, and the cells could differentiate into neurons, astrocytes and oligodendrocytes. In vitro myelin formation in neurospheres were observed at an early stage of culture. Conclusions: Human neural stem cells can be cultured from embryonic brains, can form the typical neurospheres in suspension in vitro and have the ability of myelinating, and may be potential source for transplantation in treating myelin disorders.
