We demonstrated that bone marrow (BM) stem cells are heterogenous and in addition to hematopoietic stem cells (HSC) BM also contains non-hematopoietic tissue committed stem cells (TCSC) for skeletal muscle, heart, neural tissue, epidermis and liver (
). In our follow up studies by employing multiparameter sorting we identified in murine BM a homogenous population of rare (~0.02% of BMMNC) Sca-1+ lin− CD45− cells that express by RQ-PCR and immunhistochemistry markers of pluripotent stem cells (PSC) such as SSEA-1, Oct-4, Nanog and Rex-1 and highly express Rif-1 telomerase protein. More important the direct electronmicroscopical analysis revealed that these cells display several features typical for primary embryonic stem cells such as i) small size (~3 μm in diameter), ii) poses large nuclei surrounded by a narrow rim of cytoplasm, and iii) contain open-type chromatin (euchromatin) that is typical for embryonic stem cells. Their number is highest in BM from young (1–2 month-old) mice and decreases with age. It is also significantly diminished in short living DBA/2J mice as compared to long living B6 mice. These cells in vitro respond strongly to several motomorphogens such as SDF-1, HGF and LIF and co-express the corresponding receptors such as CXCR4, c-met and LIF-R respectively on their surface. Interestingly, they adhere to fibronectin, and undergo emperipolesis in fibroblasts, thus they may be co-isolated with BM adherent cells. Furthermore, they are mobilized into peripheral blood during tissue/organ injuries (e.g., heart infarct, stroke). In in vitro cultures they differentiate into cells from different germ-layers (e.g., form neurospheres, grow cardiomyocytes). Thus, these findings support the theory of BM containing a reserve population of embryonic-like/pluripotent stem cells and it is also possible that several of the recently described BM-derived CD45− stem cell populations (e.g., MAPC, USSC or MIAMI cells) could in fact overlap with these rare non-hematopoietic CD45− stem cells identified by us, but due to the differences in the experimental approaches employed for their isolation and identification, were assigned different names. We postulate that this population of CD45− embryonic-like cells expressing pluripotent and tissue committed markers identified by us is an ideal source of cells for regeneration.
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