İskelet Kası Dejenerasyonu Sürecinde Stromal Hücre Alt Gruplarının İncelenmesi

Abstract

The characteristics of the skeletal muscle degeneration are muscle fiber atrophy and fibrosis. The genetic and cellular therapeutic approaches for skeletal muscle treatment remain incapable due to the fibrosis. Studies concerning the cellular development of fibrosis demonstrated that “Fibro/Adipogenic progenitors (FAP)” ((CD45(-), CD31(-), CD11b(-), Sca1(+), CD140a(+)), are the primary stromal cell population that causes fibrosis and their activation is related to inflammation. However, the effect of FAP cells on the fibrosis development in chronic muscle degeneration is still unknown in the absence of inflammation. In this thesis, changes of stromal cell populations including CD140a(+)/Sca1(-), CD140a(+)/Sca1(+), and CD140a(-)/Sca1(+) was examined in experimental acute muscle injury, tenotomy, and denervation models. In addition, the correlation between cell activation and inflammation was investigated. Our results showed that CD140a(+)/Sca1(+) cells drastically increased and Sca1(+)/ CD140a(-) cell population was limited cellular activation in the presence of acute muscle injury. Only CD140a(-)/Sca1(+) cell population was activated in tenotomy while CD140a(+)/Sca1(+) cells was activated in denervation. In all three experimental models, there were no significant quantitative differences in terms of CD140a(+)/Sca1(-) cell population. This thesis study proved that the activation of stromal cells in chronic degeneration model occurs inflammation-independent and the CD140a(-)/Sca1(+) cell population which is active in tenotomy and acute muscle injury is different from CD140a(+)/Sca1(+) stromal cell population. In addition, these cells have been shown to contribute fibrosis development as a result of RNA sequencing analysis.