Identification of a Discrete Population of Human Bone Marrow-Derived Mesenchymal Cells Exhibiting Properties of Uncommitted Progenitors

Abstract

Human bone marrow-derived mesenchymal progenitor cells (MPC) after ex vivo expansion give rise to a heterogeneous mixture of cells with distinct proliferative potential at various stages of differentiation. Here we show that when proliferative MPC were forced to metabolic death by exposure to 5-fluorouracil, the remaining subset (5–20%) contains a population of quiescent, uncommitted, and undifferentiated mesenchymal cells. The isolated cells self-renew and generate precursors committed at least to the adipogenic and osteogenic lineages. Taken together, these results demonstrate that within ex vivo-expanded bone marrow-derived MPC, there exist a discrete population of mesenchymal cells with properties of uncommitted progenitors. Because these cells are capable of engraftment into bone marrow, spleen, bone, and skeletal muscle after intravenous infusion and can be efficiently transduced with adenoviral vectors, they may represent an interesting option for cellular and gene therapies for a wide range of disorders of mesenchymal tissues.