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

Abstract

Evidence is presented that bone marrow (BM) in addition to CD45positive hematopoietic stem cells contains a rare population of heterogenous CD45negative nonhematopoietic tissue committed stem cells (TCSC). These nonhematopoietic TCSC (i) are enriched in population of CXCR4+ CD34+ AC133+ lin CD45 and CXCR4+ Sca-1+ lin CD45 in humans and mice, respectively, (ii) display several markers of pluripotent stem cells (PSC) and (iii) as we envision are deposited in BM early in development. Thus, since BM contains versatile nonhematopoietic stem cells, previous studies on plasticity trans-dedifferentiation of BM-derived hematopoietic stem cells (HSC) that did not include proper controls to exclude this possibility could lead to wrong interpretations. Therefore, in this spotlight review we present this alternative explanation of ‘plasticity’ of BM-derived stem cells based on the assumption that BM stem cells are heterogenous. We also discuss a potential relationship of TCSC/PSC identified by us with other BM-derived CD45negative nonhematopoietic stem cells that were recently identified by other investigators (eg MSC, MAPC, USSC and MIAMI cells). Finally, we discuss perspectives and pitfalls in potential application of these cells in regenerative medicine.

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Acknowledgements

This work was supported by an NIH Grant R01 CA106281-01 and KLCRP Grant to MZR.

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Correspondence to M Z Ratajczak.

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Supplementary Information (videos showing interaction of TCSC with BM-derived fibroblasts) accompanies the paper on the Leukemia website (http://www.nature.com/leu).

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Kucia, M., Reca, R., Jala, V. et al. Bone marrow as a home of heterogenous populations of nonhematopoietic stem cells. Leukemia 19, 1118–1127 (2005). https://doi.org/10.1038/sj.leu.2403796

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