Cells with hemopoietic potential residing in muscle are itinerant bone marrow-derived cells.

Abstract

The nature of cells residing in muscle giving rise to hemopoietic colonies in vitro or hemopoietic reconstitution in vivo has been unclear. The goal of the present study was to characterize these cells and uncover their potential site of origin. Cells prepared from muscle were characterized for surface antigens (CD45, CD34, c-kit, Sca-1, CD31, VCAM-1), for their in vitro clonogenic capacity and in vivo repopulation potential either as unpurified cells or sorted subsets (CD45(+), CD45(-)). The presence of bone marrow (BM)-derived cells in muscle of mice reconstituted with marked BM cells before and after cytokine-induced mobilization was also examined. Our data show: 1) The yield of CD45(+) cells is higher in muscle of neonates and young animals. Their composite phenotype does not favor contamination by blood. 2) The capacity of fresh muscle cell explants to give rise to colonies in vitro and hemopoietic reconstitution in vivo is associated with CD45(+) cells. 3) Irradiated recipients reconstituted with marked BM cells harbor marked BM-derived cells (CD45(+) or CD45(-)) in their muscle several months after transplant. 4) Cytokine-induced mobilization of transplanted animals modestly increases the yield of BM-derived cells recovered from muscle, unlike the yields from spleen, liver, or peripheral blood (PB). Our data suggest a reinterpretation of previously published conclusions: hemopoietic colonies derived from fresh muscle explants do not originate from transdifferentiated muscle cells, but from BM-derived cells residing in muscle; the hemopoietic reconstituting potential of muscle cells is likewise attributed to these cells.