Nature Medicine
8, 607 - 612 (2002)
doi:10.1038/nm0602-607
Adult hematopoietic stem cells provide functional hemangioblast activity during retinal neovascularizationMaria B. Grant1, 2, 3, W. Stratford May1, 2, 3, Sergio Caballero2, Gary A. J. Brown1, 3, Steven M. Guthrie1, 3, Robert N. Mames7, Barry J. Byrne6, Timothy Vaught4, Polyxenie E. Spoerri2, Ammon B. Peck1, 5
& Edward W. Scott1, 3, 61
Program in Stem Cell Biology, University of Florida, Gainesville, Florida, USA
2
Department of Pharmacology and Therapeutics, University of Florida, Gainesville, Florida, USA
3
University of Florida Shands Cancer Center, University of Florida, Gainesville, Florida, USA
4
The McKnight Brain Institute, University of Florida, Gainesville, Florida, USA
5
Department of Pathology, University of Florida, Gainesville, Florida, USA
6
Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, Florida, USA
7
The Retina Center, Gainesville, Florida, USA
Correspondence should be addressed to Maria B. Grant grantma@pharmacology.ufl.edu or Edward W. Scott escott@ufl.eduAdults maintain a reservoir of hematopoietic stem cells that can enter the circulation to reach organs in need of regeneration. We developed a novel model of retinal neovascularization in adult mice to examine the role of hematopoietic stem cells in revascularizing ischemic retinas. Adult mice were durably engrafted with hematopoietic stem cells isolated from transgenic mice expressing green fluorescent protein. We performed serial long-term transplants, to ensure activity arose from self-renewing stem cells, and single hematopoietic stem-cell transplants to show clonality. After durable hematopoietic engraftment was established, retinal ischemia was induced to promote neovascularization. Our results indicate that self-renewing adult hematopoietic stem cells have functional hemangioblast activity, that is, they can clonally differentiate into all hematopoietic cell lineages as well as endothelial cells that revascularize adult retina. We also show that recruitment of endothelial precursors to sites of ischemic injury has a significant role in neovascularization.
|
3 integrin or 
