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

Division of Experimental Hematology, St. Jude Children's Research Hospital, 332 North Lauderdale Street, Memphis, TN 38105, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 09/2004; 101(32):11761-6. DOI: 10.1073/pnas.0404626101
Source: PubMed


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 hematopoietic/osteogenic 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 osteoblasts/osteocytes 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.

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    • "Which stage in the development of marrow cells do these cells represent is difficult to say, also because they have only some features in common with other subpopulations identified in the murine bone marrow [120, 121]. It is noteworthy to mention that several studies in mice have shown that nonadherent HSPCs that can reconstitute the blood are also capable to give rise to osteoblasts [122, 123]. The Krause group has demonstrated in mice that nonhematopoietic (lin−) BM cells are the primary source of donor-derived lung epithelial cells by showing that they consistently give rise to surfactant protein C (SPC) positive lung epithelial cells in SPC-knockout recipient mice, while hematopoietic BM cells do not [124]. "
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    • "Indeed, it may or may not inXuence the choice of manipulating bone marrow aspirates, in order to obtain an adequate amount of osteogenic MSCs as an essential requirement for the success of bone tissue engineering or cell therapy. Relatively few papers have been published on this issue, and the results obtained by various authors suggest that in nonadherent bone-marrow compartment there is an undiVerentiated quiescent subpopulation of mesenchymal progenitors that may become adherent in vitro, begin to proliferate, and diVerentiate into diverse tissue lineages besides bone, as well as rescue in vivo lethally irradiated mice (Falla et al. 1993; Eipers et al. 2000; Dominici et al. 2004; Mödder and Khosla 2008; Zhang et al. 2009). Nevertheless, the diVerence among the 'early adherent' (EA), 'nonadherent' (NA), and 'late adherent' (LA) bone marrow stromal cells has not been fully elucidated. "
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