Hematopoietic Stem Cells Can Give Rise to Satellite-Like Cells in Skeletal Muscles.

Abstract

Recent studies have indicated that bone marrow cells can regenerate damaged muscles, but also that they can adopt phenotype of other cells by cell fusion. It has also been reported that single hematopoietic stem cells (HSCs) can regenerate skeletal muscle although it is still controversial whether HSCs differentiate into satellite cells in muscle or not. In order to investigate the roles of HSCs in muscle regeneration and whether they can generate satellite cells or not, we purified and injected CD45+Lin−Sca-1+c-kit+(CD45+KSL) HSCs labeled by green fluorescent protein (GFP) into mice with or without irradiation. We examined time-course behavior of HSCs in recipient muscles with a fluorescent stereomicroscope and then immunohitochemical staining during the early and late phase after transplantation. Our direct visualization system gave evidence of massive GFP signals in all the muscles of only irradiated mice in early phase after transplantation. Transverse cryostat sections showed GFP+ Myosin+ muscle fibers along with numerous GFP+ hematopoietic cells in damaged muscle. We also found myogenin+GFP+ cells like myoblasts in very low number. These phenomena were temporal and GFP signals had dramatically reduced 30 days after transplantation. FISH analysis confirmed the GFP-DNAs in the nuclei of muscle fibers. These results suggested that most of GFP+HSCs fused with myofibers and participated in regeneration of damaged muscles, and a very few HSCs can differentiate into myoblast like cells expressing myogenin. After 6 months, GFP+ fibers could be hardly detected but GFP+c-Met+ mononuclear cells were located beneath the laminin+ basal lamina. Single fiber cultures from these mice showed proliferation of GFP+ fibers. These results suggested that HSC-derived cells settled beneath the basal lamina like satellite cells and might acquired the satellite cell activity.