Adult hematopoietic stem cells provide functional hemangioblast activity during retinal neovascularization

Maria B. Grant, W. Stratford May, Sergio Caballero, Gary A.J. Brown, Steven M. Guthrie, Robert N. Mames, Barry J. Byrne, Timothy Vaught, Polyxenie E. Spoerri, Ammon B. Peck, Edward W. Scott

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591 Scopus citations

Abstract

Adults 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.

Original languageEnglish (US)
Pages (from-to)607-612
Number of pages6
JournalNature Medicine
Volume8
Issue number6
DOIs
StatePublished - Jun 25 2002

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Grant, M. B., May, W. S., Caballero, S., Brown, G. A. J., Guthrie, S. M., Mames, R. N., Byrne, B. J., Vaught, T., Spoerri, P. E., Peck, A. B., & Scott, E. W. (2002). Adult hematopoietic stem cells provide functional hemangioblast activity during retinal neovascularization. Nature Medicine, 8(6), 607-612. https://doi.org/10.1038/nm0602-607