Open AccessDifferentiation of Human Embryonic Stem Cells into Engrafting Myogenic Precursor Cells
Author(s) -
Stalin Reddy Challa,
Swathi Goli
Publication year - 2019
Publication title -
stem cell research and therapeutics international
Language(s) - English
Resource type - Journals
ISSN - 2643-1912
DOI - 10.31579/2643-1912/002
Subject(s) - myod , myogenin , embryonic stem cell , microbiology and biotechnology , stem cell , biology , transplantation , precursor cell , desmin , myocyte , immunology , myogenesis , in vitro , medicine , genetics , immunohistochemistry , gene , vimentin
Degenerative muscle diseases affect muscle tissue integrity and function. Human embryonic stem cells (hESC) are an attractive source of cells to use in regenerative therapies due to their unlimited capacity to divide and ability to specialize into a wide variety of cell types. A practical way to derive therapeutic myogenic stem cells from hESC is lacking. In this study, we demonstrate the development of two serum-free conditions to direct the differentiation of hESC towards a myogenic precursor state. Using TGFß and PI3Kinase inhibitors in combination with bFGF we showed that one week of differentiation is sufficient for hESC to specialize into PAX3+/PAX7+ myogenic precursor cells. These cells also possess the capacity to further differentiate in vitro into more specialized myogenic cells that express MYOD, Myogenin, Desmin and MYHC, and showed engraftment in vivo upon transplantation in immunodeficient mice. Ex vivo myomechanical studies of dystrophic mouse hindlimb muscle showed functional improvement one month post-transplantation. In summary, this study describes a promising system to derive engrafting muscle precursor cells solely using chemical substances in serum-free conditions and without genetic manipulation.