Dedifferentiated human umbilical cord mesenchymal stem cells participate in neurological restoration in rats with hypoxic-ischemic brain damage by reprogramming gene expression

Abstract:

Objective：To investigate the effect of transplantation of human umbilical cord mesenchymal stem cells（hUC-MSCs），neu－ronal-differentiation hUC-MSCs（Dif），neuronal-dedifferentiation hUC-MSCs（De-Dif），and neuronal-redifferentiation hUC-MSCs （Re-Dif） in the treatment of rats with hypoxic-ischemic brain damage（HIBD），and to find seed cells with better therapeutic efficiency. Methods：The hUC-MSCs were cultured in vitro，and neuronal differentiation，dedifferentiation，and redifferentiation were induced by the MNM neural induction method. The morphology of the cells in these four states was observed under a light microscope，and gene expression was analyzed by whole-gene expression profile microarray. The cells were transplanted into HIBD animals with nerve injury to perform functional detection. The gene and protein detection methods were used to investigate the possible mecha－nism of optimal seed cells. Results：Neuronal differentiation，dedifferentiation，and redifferentiation of hUC-MSCs were suc－cessfully performed in vitro. The whole-gene expression profile microarray showed reprogramming expression of genes in hUC-MSCs，Dif，De-Dif，and Re-Dif，and De-Dif and hUC-MSCs had similar gene expression patterns. The four groups of cells were trans－planted into the HIBD experimental rats，and the results showed that all four types of cells promoted neurological function recovery in HIBD rats，and De-Dif had a greater potential for nerve repair than the other three types of cells（P=0.000）. Gene ontology analysis was performed for hUC-MSCs and De-Dif，and the results showed that De-Dif was mainly involved in hypoxia response. Compared with the hUC-MSCs group，the De-Dif group had significantly higher expression of the nerve markers microtubule associated protein 2（MAP2），neuron-specific enolase（NSE），Tau，and β-tubulinⅢ and the stem genes C-MYC，NANOG，and RARβ. Conclusion：Ded－ifferentiation may regulate the expression of the nerve markers MAP2，NSE，Tau，and β-tubulinⅢ and the stem genes C-MYC，NANOG，and RARβ by reprogramming，which promotes the participation of De-Dif in HIBD nerve repair.