Pre-differentiation of human neural stem cells into GABAergic neurons prior to transplant results in greater repopulation of the damaged brain and accelerates functional recovery after transient ischemic stroke

• DOI: 10.1186/s13287-015-0175-1
• Publication Date: 2015-09-29T13:52:56Z
• Authors: Hima C. S. Abeysi...; Laita Bokhari; Anita Quigley; Mahesh Choolani; Jerry Chan; Gregory J. Dusting; Jeremy M. Crook; Nao R. Kobayashi; Carli L. Roulston
• Keywords: Repopulation; Neurosphere; Transient (computer programming)

Abstract Introduction Despite attempts to prevent brain injury during the hyperacute phase of stroke, most sufferers end up with significant neuronal loss and functional deficits. The use cell-based therapies recover injured offers new hope. In current study, we employed human neural stem cells (hNSCs) isolated from subventricular zone (SVZ), directed their differentiation into GABAergic neurons followed by transplantation ischemic brain. Methods Pre-differentiated neurons, undifferentiated SVZ-hNSCs or media alone were stereotaxically transplanted rat (n=7/group) 7 days after endothelin-1 induced stroke. Neurological outcome was assessed neurological deficit scores cylinder test. Transplanted cell survival, cellular phenotype maturation using immunohistochemistry confocal microscopy. Results Behavioral assessments revealed accelerated improvements in motor function post-transplant rats treated pre-differentiated comparison hNSC groups. Histopathology 28 days-post transplant indicated that maintained phenotype, showed evidence synaptogenesis up-regulated expression both GABA calcium signaling proteins associated neurotransmission. Rats also increased neurogenic activity within SVZ at days, suggesting an additional trophic role these cells. contrast, predominantly differentiated GFAP-positive astrocytes appeared be incorporated glial scar. Conclusion Our study is first show enhanced exogenous repopulation a stroke techniques aimed induction prior delivery resulted improved recovery.