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S. Gach, G. Malek, P. Saloupis, K. Csaky, S. W. Cousins; Increased Mesenchymal/Myofibroblast Type Cells in the "Lineage Negative" Progenitor Subset and Whole Bone Marrow of Aged Mice. Invest. Ophthalmol. Vis. Sci. 2008;49(13):4381.
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We have shown that in a model of laser-induced chorodial neovascularization (CNV) aged mice develop larger and more fibrotic lesions. The lesions contain greater frequency of smooth muscle actin expressing mesenchymal cells and pericytes than CNV in young mice. The pathology observed in aged mice can be replicated in young mice that have been reconstituted with bone marrow derived from aged mice. Therefore we hypothesize that the bone marrow of aged mice contains more mesenchymal/myofibroblast vascular progenitor cells than marrow from young mice
Using western blot we probed whole bone marrow and the "lineage negative" progenitor subset for mesenchymal and endothelial markers. The lineage negative subset was isolated using magnetic bead sorting. Mesenchymal markers used were SM22, alpha-smooth muscle actin and desmin. Endothelial markers were von Willenbrand Factor, CD31 and VE-cadherin. In vivo experiments were performed to investigate recruitment of progenitors into neovascularization using subcutaneous Matrigel implants harvested after day 10 and examined by immunohistochemistry for vascular cells with mesenchymal and endothelial markers.
The relative expression of endothelial markers in whole bone marrow and the "lineage negative" subset was the same; however, expression of mesenchymal markers was significantly increased in old marrow. We found cells expressing mesenchymal markers and endothelial markers had migrated into the matrigel. Distribution of immunopositive mesenchymal cells was greater in Matrigel implants harvested from aged mice compared to young.
The bone marrow of aged mice contains more mesenchymal/myofibroblast progenitors than the marrow of young mice. In aged mice, vascular cells that migrate into matrigel-induced neovascularization also show increased expression of mesenchymal markers. Increased fibrosis and mesenchymal-cell contribution observed in CNV appears to be replicated in neovascularization induced by subcutaneous Matrigel implants. Marrow-derived mesenchymal progenitors may play an important regulatory role in this process.
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