Intracerebral transplantation of human umbilical cord-derived mesenchymal stem cells in neonatal rat model of hypoxic-ischemic brain damage: protective effect to injured brain

Abstract:

Objective To study the brain protection and the possible mechanism of human umbilical cord-derived mesenchymal stem cells（hUC-MSCs) in neonatal rat model of hypoxic-ischemic brain damage（HIBD). Methods Successfully establishing a neonatal rat model of HIBD, hUC-MSCs labeled with BrdU were transplanted into the lateral ventricle 24 hours after HIBD. The number of apoptotic cells and the expression of Caspase-3 were detected by TUNEL and Western blot respectively at 24 and 48 hours after transplantation. The neurological functions of HIBD rats were evaluated by Longa score, and the survival, differentiation and pro-differentiation effects of hUC-MSCs were identified by immunofluorescence at 1 to 3 weeks after transplantation. Results At 24 and 48 hours after transplantation, apoptotic cells and Caspase-3 expression in the MSCs group were less than in the HIBD group（P<0.05). At 2 and 3 weeks after transplantation, the Longa score in the MSCs group was lower than in the HIBD group（P<0.05). After transplantation, positive cells labeled with BrdU were seen in the brain tissue. The expression levels of glial fibrillary acidic protein（GFAP) and neuron specific esterase（NSE) in the MSCs group were higher than in the HIBD and sham-operated control groups（P<0.05), and increased gradually with the transplantation time（P<0.05). Conclusion hUC-MSCs transplantation in HIBD rats can inhibit Caspase-3 expression and reduce apoptotic cells in the early stage, and in the later period, the survival hUC-MSCs can differentiate into neural-like cells and promote the differentiation of endogenous neural-like cells, providing protective effects to brain.