Optimizing Ex Vivo Culture of Satellite Cells

Abstract

Satellite cells are responsible for regeneration of skeletal muscles. They have the ability to form new muscle fibers and to repopulate satellite cell pool. Transplantation of human satellite cells to muscle dystrophy patients is an aim. To achieve this aim, we must understand mechanisms governing satellite cell proliferation and differentiation. We must also have tools that allow us to control these mechanisms. In this thesis, I tried to understand in vitro behavior of satellite cells and to find factors that can control their differentiation pathways. I showed the effect of in vitro culture on transcription of various myogenic regulatory factors. I also showed the effect of various inhibitors on these factors. I found that treatment of freshly isolated satellite cells and of established myoblast cells with SR1 (Stemregenin 1, one of the compounds screened at the initial part of the thesis) results in inhibition of myogenic commitment factors, MyoD and Myogenin. SR1 also succeeded to block myoblast differentiation into myotubes. SR1 treated established myoblast cells succeeded to repopulate satellite cell pool of recipient muscles. SR1 is described to work through an action on AHR (aryl hydrocarbon receptor). So, I described the expression pattern of AHR in different stages of satellite cells.