Establishment Of Human IPSC Lines From SMA Patient And Exploration The Role Of FGF During Early Stage Of IPSC Neural Differentiation

Finding cells that have a wide range of differentiation potential and self-renewal capacity are the recent focus of research in the field of regenerative medicine. Human embryonic stem cells (hESC) are one of the best candidate materials in application of stem cells, it has broad prospects in prevention and treatment of a variety of human neurological diseases. Due to ethics and immune exclusion-related issues, hESC faces enormous obstacles in clinical applications. Searching for new alternative materials should be currently one of common subject in the field of stem cell research.In recent years, as a landmark in the field of stem cells research, human induced pluripotent stem cells (iPSC), by means of application of retroviral transfection system, one or several transcription factors was transfered into adult cells, so that adult cells were reprogrammed to the iPSC which owe a wide range of differentiation potenty. The establishment of human stem cell lines based on different genetic backgrounds and multi-differentiation potential for iPSC already becomed the theoretical basis of iPSC in basic and clinical application.Spinal muscular atrophy (SMA) is a group of autosomal recessive diseases, including children's type (Ⅰ～Ⅲ) caused by gene loss of end grain side copies of SMN1 in the survival motor neuron gene (SMN), SMA showes as muscle weakness and muscle atrophy induced by degeneration of cells in spinal cord anterior horn, right now the disease has no effective treatment. The advent of iPSC technology has undoubtedly brought new hope to the SMA patients.Fibroblast growth factor (FGF) plays an important role in promoting cell proliferation and angiogenesis, related researches show that FGF can promote regeneration and repair of human's nerve. However, the role of the FGF signaling pathway in early neural differentiation of hESC or iPSC has not yet clear.Retroviral transfection system was successfully in establishing iPSC lines including a normal source and SMA patients, which were detected that wheather iPSC has similar multipotent differentiation capacity as hESC. Meanwhile we also find that FGF signaling pathway plays an important part in early neural differentiation, and some small molecule compounds can significantly improve the neural differentiation efficiency of iPSC. Our research helps to more in-depth understanding of induction and regulation of neural differentiation of iPSC and provides an ideal cell model and a solid experimental basis for the iPSC technology in the clinical treatment of SMA.