Hematopoietic cells and osteoblasts are derived from a common marrow progenitor after bone marrow transplantation

Abstract

Bone and bone marrow are closely aligned physiologic compartments, suggesting that these tissues may represent a single functional unit with a common bone marrow progenitor that gives rise to both osteoblasts and hematopoietic cells. Although reports of multilineage engraftment by a single marrow-derived stem cell support this idea, more recent evidence has challenged claims of stem cell transdifferentiation and therefore the existence of a multipotent hematopoietic͞osteogenic progenitor cell. Using a repopulation assay in mice, we show here that gene-marked, transplantable marrow cells from the plastic-nonadherent population can generate both functional osteoblasts͞osteocytes and hematopoietic cells. Fluorescent in situ hybridization for the X and Y chromosomes and karyotype analysis of cultured osteoblasts confirmed the donor origin of these cells and excluded their generation by a fusion process. Molecular analysis demonstrated a common retroviral integration site in clonogenic hematopoietic cells and osteoprogenitors from each of seven animals studied, establishing a shared clonal origin for these ostensibly independent cell types. Our findings indicate that the bone marrow contains a primitive cell able to generate both the hematopoietic and osteocytic lineages. Its isolation and characterization may suggest novel treatments for genetic bone diseases and bone injuries.

Characterization of circulating osteoblast lineage cells in humans

“…Moreover, molecular analysis demonstrated a common retroviral integration site in clonogenic hematopoietic cells and osteoprogenitors from each of seven animals studied, establishing a shared clonal origin for these cell types. These findings thus lent considerable credence to the previous work of Long et al [3,4] and established that, at least in the experimental paradigm used by Dominici and colleagues [9], non-adherent bone marrow cells have a >10-fold more robust bone-repopulating activity than do adherent bone marrow stromal cells. Moreover, the findings were also consistent with previous work by Olmsted-Davis et al [10] suggesting the presence of a unique progenitor cell with both hematopoietic and osteoblastic differentiation potential in the non-adherent subset of bone marrow cells.…”

“…The potential functional relevance of these non-adherent osteogenic bone marrow cells remained largely unexplored until recent studies by Dominici and colleagues [9], who compared hematopoietic vs. mesenchymal reconstitution of irradiated mice using either bone marrow stromal or non-adherent fractions. Thus, they obtained plastic-adherent bone marrow stromal cells from FVB/N mice and labeled them with a green fluorescent protein (GFP) marker using a retroviral vector.…”

A small interfering RNA targeting Lnk accelerates bone fracture healing with early neovascularization

“…First, osteogenesis and vasculogenesis closely regulate each other in terms of microenvironmental interaction for regenerative activity in BM. It has been reported that BM side population cells, which contain hematopoietic repopulating cells, can also engraft in the bone after transplantation 39 and that the non-adherent population of BM cells, including KSL cells, contains primitive cells able to generate both hematopoietic and osteocytic lineage cells. 40 Kwon et al 11 reported that Lnkdeficient EPCs (KSLs) are more potent in BM-EPC kinetics, including the ability of cell growth, endothelial commitment, mobilization and recruitment for vascular regeneration.…”

Bone marrow as a home of heterogenous populations of nonhematopoietic stem cells

“…Second, some evidence accumulated that BM can contain TCSC for the skeleton that are in fact distinct from BM-derived fibroblasts or MSC. 88,103 In a recently published paper, it was suggested that these osteoblastic TCSC, and not marrow fibroblasts were in fact responsible for the therapeutic effects after transplantation of BM-derived cells in children with osteogenesis imperfecta. 88 Furthermore, a very similar phenomenon of calcium or fat accumulation in cultured cells was reproduced in our laboratory with several nonfibroblastic cell lines (eg rhabdomyosarcomas and lung cancer) if these cells were cultured in the appropriate 'differentiating media' (not published).…”

“…88,103 In a recently published paper, it was suggested that these osteoblastic TCSC, and not marrow fibroblasts were in fact responsible for the therapeutic effects after transplantation of BM-derived cells in children with osteogenesis imperfecta. 88 Furthermore, a very similar phenomenon of calcium or fat accumulation in cultured cells was reproduced in our laboratory with several nonfibroblastic cell lines (eg rhabdomyosarcomas and lung cancer) if these cells were cultured in the appropriate 'differentiating media' (not published). Thus an important question emerges, if calcium or fat accumulation in cultured marrow fibroblasts is merely an effect of the pathological calcification or steatosis of cells that are exposed in vitro to high concentrations of hydrocortisone, calcium phosphate etc.…”