Research groups at Fujita Medical University and Kyoto Prefectural University of Medicine have succeeded in developing a technique for producing skeletal muscle stem cells from fibroblasts and human iPS cells.
Skeletal muscle stem cells have a mechanism in which when muscle regeneration is required, skeletal muscle is newly created and at the same time stem cells are produced again to prepare for the next regeneration.By applying this, for muscular dystrophy, which is one of the intractable muscle diseases, it is expected to develop a treatment that promotes regeneration by transplanting and replenishing stem cells, but usually in a state where it is not necessary to repair the muscle. There was the issue of how to collect non-proliferating skeletal muscular stem cells.
So far, this research group has clarified that a transcription factor called Pax3 is strongly expressed when skeletal muscle stem cells proliferate.Therefore, in this study, we investigated transcription factors that are strongly expressed in addition to Pax3 among skeletal muscle stem cells that express mouse Pax3, and as a result, four types of PAX3, MYOD, HEYL, and KLF4 were Pax-positive from mouse fibroblasts. It was found to be an essential gene for inducing skeletal muscle stem cells.
As a result, we succeeded in inducing PAX-positive skeletal muscle stem cells from mouse, human fibroblasts, and human iPS cells in about one month.When these induced human skeletal muscle stem cells were transplanted into muscular dystrophy model mice, it was confirmed that the abnormal expression of dystrophin, which causes muscular dystrophy, was dramatically recovered and greatly contributed to muscle regeneration.
This result, which revealed that skeletal muscle stem cells that are the source of skeletal muscle can be produced using four types of genes, may lead to regenerative medicine by supplementing skeletal muscle stem cells in the future.The research group is aiming to develop a technology for proliferating and culturing a large amount of inducible human skeletal muscle stem cells.
Paper information:[Stem Cell Reports] Core transcription factors promote induction of PAX3-positive skeletal muscle stem cells