1. ¹Stem Cell Biology Program at James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA
2. ²Department of Neurosurgery, University of Louisville, Louisville, KY, USA
3. ³Institute of Cellular Therapeutics, University of Louisville, Louisville, KY, USA
4. ⁴European Union Stem Cell Therapeutics Excellence Centre, CMUJ Crown, Poland

Correspondence: Dr MZ Ratajczak, Stem Cell Biology Program, University of Louisvillem 580 S Preston St, Baxter II, Rm. 119E, Louisville, KY 40202, USA. E-mail: mzrata01@louisville.edu

Received 22 March 2005; Revised 23 August 2005; Accepted 20 September 2005; Published online 3 November 2005.

Abstract

The concept that bone marrow (BM)-derived cells participate in neural regeneration remains highly controversial and the identity of the specific cell type(s) involved remains unknown. We recently reported that the BM contains a highly mobile population of CXCR4⁺ cells that express mRNA for various markers of early tissue-committed stem cells (TCSCs), including neural TCSCs. Here, we report that these cells not only express neural lineage markers (-III-tubulin, Nestin, NeuN, and GFAP), but more importantly form neurospheres in vitro. These neural TCSCs are present in significant amounts in BM harvested from young mice but their abundance and responsiveness to gradients of motomorphogens, such as SDF-1, HGF, and LIF, decreases with age. FACS analysis, combined with analysis of neural markers at the mRNA and protein levels, revealed that these cells reside in the nonhematopoietic CXCR4⁺/Sca-1⁺/lin^-/CD45^- BM mononuclear cell fraction. Neural TCSCs are mobilized into the peripheral blood following stroke and chemoattracted to the damaged neural tissue in an SDF-1-CXCR4^-, HGF-c-Met^-, and LIF-LIF-R-dependent manner. Based on these data, we hypothesize that the postnatal BM harbors a nonhematopoietic population of cells that express markers of neural TCSCs that may account for the beneficial effects of BM-derived cells in neural regeneration.