The identification of embryonic-like SSEA+ OCT-4+ CXCR4+ stem cells in adult bone marrow and cord blood

Mariusz Z. Ratajczak 1,2Magdalena Kucia 2Bogusław B. Machaliński 1

1. Department of Physiopathology, Pomeranian Medical University (PAM), Powstancow Wlkp. 72, Szczecin 70-111, Poland
2. Stem Cell Biology Program at James Graham Brown Cancer Center, University of Louisville, Louisville 40202, United States

Abstract

Several lines of evidence support the presence of pluripotent stem cells (PSC) in adult bone marrow (BM) and cord blood (CB). To support this, the expression of typical PSC markers Oct-4 and Nanog (embryonic stem cells transcription factors) and SSEA (stage specific embryonic antigen) was reported at the protein and/or mRNA level in BM- and CB-derived stem cells. Accordingly, these embryonic markers were demonstrated in described by our team very small embryonic-like (VSEL) stem cells isolated from the adult bone marrow and cord blood (Leukemia 2006;20:857-869 & Leukemia 2007;21:297-303), multipotent adult progenitor cells (MAPC), mesenchymal stem cells (MSC) and marrow-isolated adult mulitlineage inducible (MIAMI) cells.

In addition to BM and CB, recently several groups reported the presence of Oct-4+ cells in epidermis, heart, pancreas, testis, and bronchial epithelium. Since SSEA, Oct-4 and Nanog are the markers characteristic for embryonic stem cells (ESC), epiblast stem cells (EPSC) and primordial germ cells (PGC), the presence of these cells in adult tissues supports the concept that adult tissues contain some population of PSC that is deposited in embryogenesis during early gastrulation. We hypothesize that these cells could be direct descendants of the germ lineage. The germ lineage in order to pass genes on to the next generations creates soma and thus becomes a “mother lineage” for all somatic cell lineages present in the adult body. We also hypothesize that similarly as PGC, PSC deposited in the developing tissues undergo erasure of their somatic imprint. This mechanism of erasure will protect developing organism from the possibility of teratoma formation. However, it also affects some of the aspects of the “true pluripotentiality” of these cells (e.g., their potential to complete blastocyst development).

We postulate that these Oct-4+ PSC play a role in steady state conditions in tissue turnover (e.g., as source of long term hematopoiesis repopulating cells). Furthermore, during organ damage (e.g., heart infarct or stroke) these cells could be mobilized from the BM and perhaps other tissue specific niches into peripheral blood where they circulate in order to “home” to damaged organs and participate in their repair (Circulation 2004, 110, 3213-3220, Cir. Research 2004, 95, 1191-1199, Exp. Hematol. 2005, 33, 613-623, Leukemia 2006, 20, 18-28). On other hand they may be also a source of malignancies. Accordingly, if these cells i) do not erase somatic imprint, ii) go astray from the major migratory routes, iii) acquire critical mutations or iv) if mobilized at the wrong time into peripheral blood, and deposited in areas of chronic inflammation, instead of playing a role in regeneration may contribute to the development of malignancies (e.g., teratomas, germinomas, pediatric sarcomas and development of other tumors respectively) (Stem Cells 2005, 23, 879-894, Leukemia 200, 21, 860-867).

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Presentation: Wykład at Zjazd Polskiego Towarzystwa Biochemicznego, Sympozjum C, by Bogusław B. Machaliński
See On-line Journal of Zjazd Polskiego Towarzystwa Biochemicznego

Submitted: 2007-05-08 10:05
Revised:   2009-06-07 00:44
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