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Transplantation of neural stem cells from different sources in the treatment of cerebral ischemia injury in rats

BACKGROUND: The underlying mechanism of neurological dysfunction caused by cerebral ischemia is neuronal damage, and facilitating neuronal regeneration is the key to neural function recovery. However, endogenous neural stem cells have limited use in nerve repair. Transplantation of exogenous neural stem cells brings hope for tissue remodeling and functional recovery after cerebral ischemia, but systematic comparative studies on the selection of seed cells are still lacking. OBJECTIVE: To compare the therapeutic effect of neural stem cells from three sources in the treatment of cerebral ischemia injury in rats. METHODS: Adipose-derived mesenchymal stem cells (ADMSCs), bone marrow mesenchymal stem cells (BMSCs), and skin-derived induced pluripotent stem cells (iPSCs) from Sprague-Dawley rats were isolated and cultured, and induced in vitro to differentiate into neural stem cells. Conversion efficiency was detected at 7 days of neuronal induction. One hundred rat models of cerebral ischemia were randomized into model, BMSCs, iPSCs, ADMSCs, and PBS groups, with 20 rats in each group. Then, corresponding cell suspension or PBS solution was transplanted in each group. Another 40 Sprague-Dawley rats were taken as sham operation group (n=20) and control group (n=20) with no intervention. Index measurements were performed at 1 and 4 weeks after cell transplantation. RESULTS AND CONCLUSION: After 7 days of in vitro induction, the conversion efficiency of iPSCs was significantly higher than that of ADMSCs and BMSCs (P < 0.01). At 1 and 4 weeks after transplantation, neuronal apoptosis and infarction size were significantly reduced in the iPSCs, ADMSCs and BMSCs groups as compared with the PBS and model groups (P < 0.05). Moreover, neurological severity score, infarction size and neuronal apoptosis were significantly reduced in the iPSCs group as compared with the ADMSCs and BMSCs groups (P < 0.05). At 4 weeks after cell transplantation, neurological severity score, infarction size and neuronal apoptosis in each group showed significant reduction as compared with the values at 1 week after cell transplantation (P < 0.01). Numbers of Nissl bodies in neurons of the striatum in the three cell transplantation groups were significantly higher than those in the control and sham operation groups. Our findings from this study reveal that neural stem cells differentiated from three sources can significantly improve the symptoms of neurological deficits, and reduce infarction size, neuronal degeneration and neuronal apoptosis. iPSCs especially have better differentiation ability and therapeutic effects than BMSCs and ADMSCs. Subject headings: Mesenchymal Stem Cells; Bone Marrow; Adipose Tissue; Induced Pluripotent Stem Cells; Neural Stem Cells; Cell Differentiation; Brain Infarction; Tissue Engineering