Contribution of bone marrow-derived pericyte precursor cells to corneal vasculogenesis.
OBJECTIVE
Bone-marrow (BM)-derived hematopoietic precursor cells are thought to participate in the growth of blood vessels during postnatal vasculogenesis. In this investigation, multichannel laser scanning confocal microscopy and quantitative image analysis were used to study the fate of BM-derived hematopoietic precursor cells in corneal neovascularization.


METHODS
A BM-reconstituted mouse model was used in which the BM from enhanced green fluorescent protein (GFP)-positive mice was transplanted into C57BL/6 mice. Basic fibroblast growth factor (bFGF) was used to induce corneal neovascularization in mice. The vasculogenic potential of adult BM-derived cells and their progeny were tested in this in vivo model. Seventy-two histologic sections selected by systematic random sampling from four mice were immunostained and imaged with a confocal microscope and analyzed with image-analysis software.


RESULTS
BM-derived endothelial cells did not contribute to bFGF-induced neovascularization in the cornea. BM-derived periendothelial vascular mural cells (pericytes) were detected at sites of neovascularization, whereas endothelial cells of blood vessels originated from preexisting blood vessels in limbal capillaries. Fifty three percent of all neovascular pericytes originated from BM, and 47% of them originated from preexisting corneoscleral limbus capillaries. Ninety-six percent and 92% of BM-derived pericytes also expressed CD45 and CD11b, respectively, suggesting their hematopoietic origin from the BM.


CONCLUSIONS
Pericytes of new corneal vessels have a dual source: BM and preexisting limbal capillaries. These findings establish BM as a significant effector organ in corneal disorders associated with neovascularization.
Ozerdem
Ugur
U
La Jolla Institute for Molecular Medicine, CA 92121, USA. ozerdem@ljimm.org
Alitalo
Kari
K
Salven
Petri
P
Li
Andrew
A
D000818:Animals; D039481:CD11b Antigen / Q000378:metabolism; D016510:Corneal Neovascularization / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D004195:Disease Models, Animal; D004729:Endothelium, Lymphatic / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000633:toxicity; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology*; D007150:Immunohistochemistry; D017493:Leukocyte Common Antigens / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D020286:Pericytes / Q000166:cytology / Q000502:physiology*
D039481:CD11b Antigen; C485184:enhanced green fluorescent protein; D016222:Fibroblast Growth Factor 2; D049452:Green Fluorescent Proteins; D017493:Leukocyte Common Antigens