Cells enriched in markers of neural tissue-committed stem cells reside in the bone marrow and are mobilized into the peripheral blood following stroke.
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 (beta-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.
Kucia
M
M
Stem Cell Biology Program at James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA.
Zhang
Y P
YP
Reca
R
R
Wysoczynski
M
M
Machalinski
B
B
Majka
M
M
Ildstad
S T
ST
Ratajczak
J
J
Shields
C B
CB
Ratajczak
M Z
MZ
D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000166:cytology* / Q000502:physiology; D019070:Cell Lineage; D002465:Cell Movement; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000096:biosynthesis; D005260:Female; D017228:Hepatocyte Growth Factor / Q000096:biosynthesis; D066298:In Vitro Techniques; D015850:Interleukin-6 / Q000096:biosynthesis; D053605:Leukemia Inhibitory Factor; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D019718:Receptors, CXCR4 / Q000502:physiology; D012038:Regeneration / Q000502:physiology; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology; D020521:Stroke / Q000503:physiopathology*
D000943:Antigens, Differentiation; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D012333:RNA, Messenger; D019718:Receptors, CXCR4; D017228:Hepatocyte Growth Factor