Abstract 85: Human Neuronal Cells Directly Induced From Human Skin Fibroblasts: A Novel Cell Resource For Stroke Therapy
Strokes induce tremendous neuronal death, are a major cause of death and reduce the quality of life. Induced pluripotent stem cell methods, which supply neuronal cells, may provide cures for various neurological diseases including stroke, although their tumorigenicity interferes with clinical applications. To induce neuronal cells without passing the pluripotent state, we tried to convert human skin fibroblasts to human-induced neuronal (hiN) cells by viral cotransduction of a combination of five neuron specific transcription factors, Ascl1, Brn2, Myt1l, Olig2, and Zic1. Three weeks after viral transduction, we found these hiN cells were positive for neuronal markers, including Tuj1, MAP2, Tau1, and NeuN, and showed a neuronal morphology. We also confirmed that the hiN cell phenotype can be achieved without expression of the progenitor/stem cell markers Sox2, Pax6, Otx2, or FoxG1 during hiN cell reprogramming. Of note, we demonstrated that GFP-labeled hiN cells, which were transplanted in utero into an embryonic day 13.5 mouse brain, could migrate from the ventricles into various brain regions. Moreover, the results of voltage-clamp recordings from hiN cells within acutely prepared brain slices indicated that hiN cells can make functional neuronal connections with the surrounding neuronal circuit in vivo. Taken together, these results suggest that this novel hiN method can supply functional neuronal cells from human skin fibroblasts without passing through the progenitor/pluripotent state. Here, we propose that hiN cells can be a promising cell source for cell transplantation therapy to stroke patients.
- © 2012 by American Heart Association, Inc.