Chemical Conversion Of Mouse Fibroblasts To Functional Dopaminergic Neurons And Schwann Cells

Ectopic expression of lineage-specific transcription factors facilitates the conversion of mammalian somatic cells into dopaminergic(DA)neurons,which is a promising strategy for cell therapy of Parkinson's disease(PD).However,this approach still has some drawbacks limiting its clinical application due to the potential risks of integrating vectors into the host genome.Therefore,it is critical to seek a more desired approach to generate DA neurons derived from mammalian somatic cells.Here,we reported that mouse embryonic fibroblasts(MEFs)can be efficiently converted into DA neurons by using small molecules along with specific growth factors,as demonstrated by several assessments.These neuron-like cells generated a neuronal morphology,and acquired immunocytochemical and calcium imaging special for neuronal electrophysiological profile.More importantly,these converted cells can secrete dopamine,indicating that they are functionally similar to DA neurons.Taken together,our study might provide a promising cell source for treating PD by using small molecule-mediate approach without introduction of exogenous transcription factors.Spinal Cord Injury(SCI)is caused by trauma,inflammation,tumor and other reasons.The traverse injury will bring about motional,sensory,sphincter and autonomous nervous dysfunction.According to recent researches,researchers have demonstrated that Schwann cells(SC)could facilitate the regeneration of neuron by secreting growth factors.There are two ways to generate Schwann cells,one is differentiation of embryonic stem cells or induced pluripotent cells;another is conversion of fibroblasts into Schwann cells.Here,we reported that mouse embryonic fibroblasts(MEFs)could be converted to Schwann cells by chemical molecules and growth factors.By immunostaining and Q-PCR of S100? and PLP,which are markers of Schwann cells,the converted cells were found to be similar with Schwann cells in terms of immunocytochemic,and gene expression levels.In total,our induction strategy,combining inhibitors and growth factors,could realize the conversion of MEF to Schwann cells.Additionally,this method would be a promising treatment for Spinal Cord Injury.