Abstract

We have previously demonstrated that adult HSC produce circulating endothelial progenitor cells (EPC) in response to ischemic injury. We utilize a model of neovascularization in the murine retina that results in high levels of HSC-derived contribution in the new vessels. Our preliminary data and that from other labs suggest that the degree of ischemic damage dictates the overall level of HSC contribution to new vessels. Recent work also suggests that new vessel formation results from an interplay between HSC-derived EPC and circulating endothelial cells (EC) derived from existing vessels. In this renewal application we will extend of previous work to examine what differing roles of HSC-derived EPC and vessel-derived EC in new vessel generation and existing vessel repair. We will also test potential mechanisms to promote EPC driven vessel formation/repair and the role hypoxia and hypoxia regulated factors in HSC production of EPC. The purpose of this proposal is to define the role of hematopoietic cells in new blood vessel formation and damaged vessel repair. Preclinical data for the prevention of proliferative retinopathy and cardiovascular disease will lay the groundwork for phase I clinical trails. PUBLID

Public Health Relevance

The purpose of this proposal is to define the role of hematopoietic cells in new blood vessel formation and damaged vessel repair. Preclinical data for the prevention of proliferative retinopathy and cardiovascular disease will lay the groundwork for phase I clinical trails.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL070738-08
Application #
8055386
Study Section
Special Emphasis Panel (ZRG1-HEME-D (02))
Program Officer
Thomas, John
Project Start
2002-07-01
Project End
2013-03-31
Budget Start
2011-04-01
Budget End
2013-03-31
Support Year
8
Fiscal Year
2011
Total Cost
$366,250
Indirect Cost

  Institution

Name
University of Florida
Department
Genetics
Type
Schools of Medicine
DUNS #
969663814
City
Gainesville
State
FL
Country
United States
Zip Code
32611

  Publications

Kim, S; Lin, L; Brown, G A J et al. (2017) Extended time-lapse in vivo imaging of tibia bone marrow to visualize dynamic hematopoietic stem cell engraftment. Leukemia 31:1582-1592
Cogle, Christopher R; Goldman, Devorah C; Madlambayan, Gerard J et al. (2014) Functional integration of acute myeloid leukemia into the vascular niche. Leukemia 28:1978-1987
Pi, Liya; Shenoy, Anitha K; Liu, Jianwen et al. (2012) CCN2/CTGF regulates neovessel formation via targeting structurally conserved cystine knot motifs in multiple angiogenic regulators. FASEB J 26:3365-79
Shenoy, Anitha K; Fisher, Robert C; Butterworth, Elizabeth A et al. (2012) Transition from colitis to cancer: high Wnt activity sustains the tumor-initiating potential of colon cancer stem cell precursors. Cancer Res 72:5091-100
Pi, Liya; Xia, Huiming; Liu, Jianwen et al. (2011) Role of connective tissue growth factor in the retinal vasculature during development and ischemia. Invest Ophthalmol Vis Sci 52:8701-10
Bengtsson, N E; Kim, S; Lin, L et al. (2011) Ultra-high-field MRI real-time imaging of HSC engraftment of the bone marrow niche. Leukemia 25:1223-31
Madlambayan, Gerard J; Meacham, Amy M; Hosaka, Koji et al. (2010) Leukemia regression by vascular disruption and antiangiogenic therapy. Blood 116:1539-47
Carpentino, Joseph E; Hynes, Mark J; Appelman, Henry D et al. (2009) Aldehyde dehydrogenase-expressing colon stem cells contribute to tumorigenesis in the transition from colitis to cancer. Cancer Res 69:8208-15
Kim, M; Madlambayan, G J; Rahman, M M et al. (2009) Myxoma virus targets primary human leukemic stem and progenitor cells while sparing normal hematopoietic stem and progenitor cells. Leukemia 23:2313-7
Madlambayan, Gerard J; Butler, Jason M; Hosaka, Koji et al. (2009) Bone marrow stem and progenitor cell contribution to neovasculogenesis is dependent on model system with SDF-1 as a permissive trigger. Blood 114:4310-9

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