Human neural stem cells over-expressing Akt1 provide cytoprotection and functional recovery in mouse stroke model
Akt1 (protein kinase B), a serine/threonine kinase, has emerged as a critical molecule in signal transduction pathways involved in cell proliferation, growth, survival, apoptosis and glucose metabolism. A previous study has shown that transplanted human neural stem cells (hNSCs) selectively migrate to the brain and induce behavioral recovery in mouse intracerebral hemorrhage (ICH) stroke model. However, many of the grafted hNSCs did not survive the transplantation, which may have reduced therapeutic potential. In this study, we postulated that hNSCs over-expressing Akt1 transplanted into the lesion could improve survival of grafted hNSCs and behavioral recovery in mouse ICH model. To establish Akt1 over-expressing hNSC line, F3 hNSCs were transduced with retroviral vectors containing mouse Akt1 cDNA. We examined the viability of Akt1 over-expressing hNSCs against to the H2O2-induced cell death and oxygen glucose deprivation (OGD) condition in vitro. F3.Akt1 cells were showed more resistance to the cell death stimuli. To investigate the therapeutic effects in vivo, ICH was induced in adult mice by unilateral injection of bacterial collagenase into striatum and then, we transplanted F3 and F3.Akt1 hNSCs into the animal brain. Transplantation of F3.Akt1 hNSCs increased survival of grafted cells by 0.5 ？ 2 fold at two weeks and eight weeks, and induced behavioral improvement in animals. These results demonstrate that the over expression of Akt1 supports the prolonged survival of the engrafted cells and protects hNSCs from cell death by the inhibitory death machinery activation.
human neural stem cells, transplantation, Akt1, 마우스 뇌출혈 뇌졸중, 인간 신경줄기
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