Investigation of neurokine-mediated neuronal differentiation of human fibroblast / induced pluripotent stem cells (hiPSCs)-derived neuronal stem cells (NSCs)

Abstract

iPSC has opened the possibility for personalized regenerative treatment via autologous transplantation from patient’s own tissue that can open avenues to treat neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and other related degenerative diseases. However, the practical application for neural cell replacement is limited by heterogeneity of neural stem cell (NSC) progeny, relatively low yield of neurons, predominance of astrocytes, poor survival of donor cells following transplantation and the potential for uncontrolled proliferation of precursor cells. Previous study has shown that Hyper interleukin-6 (HIL-6), a fusion protein of interleukin (IL-6) and its soluble receptor sIL-6R have neurogenic activity via sole activation of mitogen activated protein kinase (MAPK) pathway. Therefore in this study we want to investigate the application of IL-6 and sIL-6R for inducing neurogenesis on human iPSC-derived NSCs. In the present study, we found that activating IL-6 signaling can be used to improve neuron yield of iPSC-derived NSC and the obtained neuron can be FACS purified to generate pure neural population that can be used for further IL-6 signaling study in iPSC development model or as a source for regenerative therapy to tackle the challenge of incurable neurodegenerative disease, such as AD or PD. Unlike the previous findings that reported activation of IL-6/STAT3 axis to be gliogenic, this study demonstrated that IL-6 activation is neurogenic to the level comparable with BDNF and the addition of STAT3 specific inhibitor abolished the neurogenicity of IL-6.