1. ¹Stem Cell Biology Program at James Graham Brown Cancer Center, University of Louisville, KY, USA
2. ²European Stem Cells Therapeutics Excellence Center, CMUJ, Cracow, Poland

Correspondence: Professor MZ Ratajczak, Stem Cell Biology Program, James Graham Brown Cancer Center, University of Louisville, KY 40202, USA. Fax: +1 502 852 3032; E-mail: mzrata01@louisville.edu

Received 12 January 2005; Accepted 4 April 2005; Published online 19 May 2005.

Abstract

Evidence is presented that bone marrow (BM) in addition to CD45^positive hematopoietic stem cells contains a rare population of heterogenous CD45^negative 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 CD45^negative 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.