Neural Stem Cells Reprogrammed From Human Umbilical Cord Mesenchymal Stem Cells

Neurodegenerative disease is a kind of neural degenerative diseases or neuronapoptosis disease,that lead to the individual behavior and even the death.Due to the limited self-repair ability of the central nervous system,makes cell replacement therapy become a effective method to restore nervous system functions through replace damaged organizational structure of the nervous system.Induced Neural stem cells (iNSCs) are able to self-renewal and differentiation into neurons and glialcells, and can release neurotrophic factors and growth factors that provide nutrition for neurocyte,it plays an important role in treated theneurodegenerative diseases by replace damaged nerve cells.It’s an ideal cell resources of cell replacement therapy Neurodegenerative disease.Since 2006,the mouse embryonic fibroblast is induced into induced pluripotent stem cells (iPSCs),the reprogramming of somatic cells has become a potential and valuable tools in the field of regenerative medicine.Reprogramming adult stem cells(mesenchymal stem cells)into neural stem cells and transplantation therapy neurodegenerative disease has become a new treatment strategy.In the process of adult cells reprogrammed to neural stem cells,SOX2 plays an important role which is able to activate the reprogramming process of adult cells to neural stem cells.Mbd3 is required for early embryonic development,pluripotency of embryonic stem cells and induced pluripotent cells development.In this study,we isolated and cultured human umbilical cord Mesenchymal stem cells (hUC-MSCs),induced hUC-MSCs transdifferentation into induced Neural stem cells by recombinant lentivirus down-regulated Mbd3 and expressed transcription factor SOX2,and identified the biological activity.Experimental results show that the isolated and cultured hUC-MSCs had the same surface antigen types as reported in some papers and multi-direction differentiation potential.SOX2 was successfully transcripted and expressed in hUC-MSCs after infected by recombinant lentivirus pLV-EGFP-SOX2-2A,The transcription and expression of Mbd3 was successfully down-regulated in hUC-MSCs after infected by recombinant lentivirus pLVMbd3shRNA-EGFP-2A.The induction experimental results show that SOX2 alone induced group and siMbd3+SOX2 induced group can detected the transcription and expression of neural stem cell specific gene, but siMbd3+SOX2 induced group success rate was obviously higher than SOX2 alone induced group.Induced iNSC differentiation into nerve cells,the results show that iNSCs can different to neurons and astrocyte.The study found that remove Mbd3 and express SOX2, hUC-MSCs can differentiate into neural stem cells, and have the ability of differentiate into nerve cells,like astrocyte and neuron,in the process, transcription factors SOX2 activate hUC-MSCs transdifferentation to neural stem cell,down-regulating Mbd3 transcription and expression can improve the efficiency and success rate of differentiation.The purpose of this study is finding an efficient method to induce hUC-MSCs differentiate into neural stem cells in vitro,and provide the scientific basis and ideas for cell replace therapy neurodegenerative disease.