We have proven that the adult hematopoietic stem cell (HSC) is able to function as a hemangioblast. Using a unique model of adult retinal neovascularization, we performed a series of experiments to ask if adult HSC exhibit hemangioblast activity by contributing to both blood and blood vessel repair in response to ischemic injury. Bone marrow transplant recipients were durably reconstituted with a single donor HSC from congenic mice expressing Gfp. Ischemia was induced in one retina per animal. Physiological localization of marrow-derived progeny to retina was detected by confocal microscopy of newly differentiated vascular tufts composed of Gfp* endothelial cells. Both FACS and fluorescent microscopy confirmed full multilineage hematopoietic reconstitution of the transplant recipients. This study is the first to prove that an adult stem cell can exhibit functional plasticity in a transplant setting. In this proposal we seek to utilize this unique model to address the following hypotheses:
Aim 1. Hypothesis: Remodeling of the endothelial niche by hemangioblast activity is the initial step in bone marrow remodeling following bone marrow transplant.
Aim 2. Hypothesis: HSChemangioblast activity produces a developmental hierarchy of cells with the potential to differentiate into endothelial cells. With our model we can define the lineage relationships and phenotypes of this new hematopoietic activity.
Aim 3. Hypothesis: HSCare the source of circulating endothelial progenitors. Therefore, factors that affect HSCor leukocyte migration will affect EPCproduction and recruitment.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL075258-03
Application #
7369783
Study Section
Special Emphasis Panel (ZRG1-HEME-D (02))
Program Officer
Gao, Yunling
Project Start
2006-03-15
Project End
2010-02-28
Budget Start
2008-03-01
Budget End
2009-02-28
Support Year
3
Fiscal Year
2008
Total Cost
$441,297
Indirect Cost
Name
University of Florida
Department
Genetics
Type
Schools of Medicine
DUNS #
969663814
City
Gainesville
State
FL
Country
United States
Zip Code
32611
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