Differential healing activities of CD34+ and CD14+ endothelial cell progenitors.
OBJECTIVE
Peripheral blood contains primitive (stem cell-like) and monocytic-like endothelial cell progenitors. Diabetes apparently converts these primitive progenitors, from a pro-angiogenic to anti-angiogenic phenotype. Monocytic progenitors seem to be less affected by diabetes, but potential pro-angiogenic activities of freshly isolated monocytic progenitors remain unexplored. We compared the ability of primitive and monocytic endothelial cell progenitors to stimulate vascular growth and healing in diabetes and investigated potential molecular mechanisms through which the cells mediate their in vivo effects.


RESULTS
Human CD34+ primitive progenitors and CD14+ monocytic progenitors were injected locally into the ischemic limbs of diabetic mice. CD14+ cell therapy improved healing and vessel growth, although not as rapidly or effectively as CD34+ cell treatment. Western blot analysis revealed that cell therapy modulated expression of molecules in the VEGF, MCP-1, and angiopoietin pathways.


CONCLUSIONS
Injection of freshly isolated circulating CD14+ cells improves healing and vascular growth indicating their potential for use in acute clinical settings. Importantly, CD14+ cells could provide a therapeutic option for people with diabetes, the function of whose CD34+ cells may be compromised. At least some progenitor-induced healing probably is mediated through increased sensitivity to VEGF and increases in MCP-1, and possibly modulation of angiopoietins.
Awad
Ola
O
Department of Anatomy and Cell Biology, University of Iowa, Iowa City, IA 52242, USA.
Dedkov
Eduard I
EI
Jiao
Chunhua
C
Bloomer
Steven
S
Tomanek
Robert J
RJ
Schatteman
Gina C
GC
D000818:Animals; D018952:Antigens, CD34; D002454:Cell Differentiation; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000473:pathology / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000473:pathology / Q000502:physiology*; D005121:Extremities / Q000098:blood supply; D006412:Hematopoietic Stem Cells / Q000473:pathology / Q000502:physiology*; D006801:Humans; D007511:Ischemia / Q000628:therapy; D018950:Lipopolysaccharide Receptors; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009000:Monocytes / Q000473:pathology / Q000502:physiology*; D018919:Neovascularization, Physiologic; D033581:Stem Cell Transplantation; D014945:Wound Healing
D018952:Antigens, CD34; D018950:Lipopolysaccharide Receptors