Recent findings of endothelial progenitor cell activity in the bone marrow and peripheral blood has generated considerable interest in the role of these cells in maintaining and repairing blood vessels. The identity of these cells and the full potential of their functional activity are not well understood. Studies from our laboratory demonstrate that a single cell from a highly purified population of adult hematopoietic stem cells (HSC) can differentiate into endothelial cells and blood cells. We hypothesize that the existence of an HSC derived endothelial progenitor cell population in normal bone marrow. The identification and functional characterization of these bone marrow derived cells is necessary to further understand their contribution to the maintenance of the vascular endothelium. The objective of this proposal is to evaluate the functional potential of bone marrow derived endothelial precursor cell populations in the bone marrow, blood and peripheral tissues. To accomplish this we will determine the role of these endothelial progenitors in maintaining the integrity of the vascular endothelium and the response of these progenitor cells to proangiogenic signals. Specifically we propose to: 1) Determine the endothelial cell potential of phenotypically defined subsets of normal adult bone marrow cells; 2) Evaluate the origin and functional activity of circulating endothelial progenitor cells and 3) Determine the capacity of bone marrow derived endothelial progenitor cells to enhance angiogenesis. These studies will identify bone marrow derived endothelial progenitors that in the future may be targeted to enhance vascular repair and to attenuate the progression of vascular disease.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL077818-01A1
Application #
6924895
Study Section
Hematopoiesis Study Section (HP)
Program Officer
Thomas, John
Project Start
2005-04-01
Project End
2009-03-31
Budget Start
2005-04-01
Budget End
2006-03-31
Support Year
1
Fiscal Year
2005
Total Cost
$315,000
Indirect Cost
Name
Oregon Health and Science University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
096997515
City
Portland
State
OR
Country
United States
Zip Code
97239
Smith, M Shane; Goldman, Devorah C; Bailey, Alexis S et al. (2010) Granulocyte-colony stimulating factor reactivates human cytomegalovirus in a latently infected humanized mouse model. Cell Host Microbe 8:284-91
Zhang, Qing-Shuo; Marquez-Loza, Laura; Eaton, Laura et al. (2010) Fancd2-/- mice have hematopoietic defects that can be partially corrected by resveratrol. Blood 116:5140-8
Li, Bei; Bailey, Alexis S; Jiang, Shuguang et al. (2010) Endothelial cells mediate the regeneration of hematopoietic stem cells. Stem Cell Res 4:17-24
Kampa, Kerstin M; Acoba, Jared D; Chen, Dexi et al. (2009) Apoptosis-stimulating protein of p53 (ASPP2) heterozygous mice are tumor-prone and have attenuated cellular damage-response thresholds. Proc Natl Acad Sci U S A 106:4390-5
Goldman, Devorah C; Bailey, Alexis S; Pfaffle, Dana L et al. (2009) BMP4 regulates the hematopoietic stem cell niche. Blood 114:4393-401
Liu, Hui; Huang, Jing; Wang, Jin et al. (2008) Transvection mediated by the translocated cyclin D1 locus in mantle cell lymphoma. J Exp Med 205:1843-58
Jiang, Shuguang; Bailey, Alexis S; Goldman, Devorah C et al. (2008) Hematopoietic stem cells contribute to lymphatic endothelium. PLoS One 3:e3812
Spangrude, Gerald J; Cho, Scott; Guedelhoefer, Otto et al. (2006) Mouse models of hematopoietic engraftment: limitations of transgenic green fluorescent protein strains and a high-performance liquid chromatography approach to analysis of erythroid chimerism. Stem Cells 24:2045-51
Rizvi, Adnan Z; Swain, John R; Davies, Paige S et al. (2006) Bone marrow-derived cells fuse with normal and transformed intestinal stem cells. Proc Natl Acad Sci U S A 103:6321-5
Bailey, Alexis S; Willenbring, Holger; Jiang, Shuguang et al. (2006) Myeloid lineage progenitors give rise to vascular endothelium. Proc Natl Acad Sci U S A 103:13156-61

Showing the most recent 10 out of 11 publications