Hematopoietic progenitors and stem cells in skeletal muscle

摘要

It was reported that mononuclear cells (MNC) harvested from skeletal muscle are capable of hematopoietic reconstitution. First, we investigated hematopoietic capabilities of MNC harvested from skeletal muscle of C57BL/6-Ly-5.1 mice by means of clonal cell culture and transplantation into lethally irradiated Ly-5.2 mice. Muscle MNC contained colony-forming cells and long-term engrafting cells, as reported previously. Next, we examined the nature of the hematopoietic progenitors in the muscle using methylcellulose culture. The types and incidences of colonies grown from the muscle MNC were different from those cultured from bone marrow (BM) or peripheral blood MNC. We then examined the origin of the hematopoietic progenitors and stem cells in the muscle by using Ly-5.2 mice that had been made chimeric by transplantation of Ly-5.1 BM cells. The percentages of Ly-5.1 cells cultured from the muscle of the chimeric mice correlated with those cultured from BM, indicating BM origin of hematopoietic progenitors in the muscle. Long-term hematopoietic engrafting cells in the muscle of the chimeric mice were also derived from BM. However, mobilization of progenitors into circulation by granulocyte colony-stimulating factor did not change the population of hematopoietic progenitors in the muscle. We then separated muscle MNC by FACS sorting into CD45(+) cells and CD45(-) cells, and analyzed their hematopoietic capability in vitro and in vivo. The hematopoielic progenitors and stem cells were present only in the CD45(+) fraction. Together, it is proposed that hematopoietic progenitors and stem cells in the muscle tissue are derived from BM CD45(+) hematopoietic populations but their transition from BM to muscle may be a slow process.