Bone marrow derived stem cells are under intense study as potential therapeutic agents for a wide variety of pathologies. Treatment with exogenous bone marrow cells can improve myocardial function after infarct and brain function after stroke in rodents. Despite tremendous progress in the development of potential clinical uses of bone marrow stem cells, little is known about their normal in vivo functions or factors controlling their growth and differentiation. Further, nothing is known about the changes that occur in these cells once they move from the bone marrow to the blood, yet it is thought that the cells must travel through the blood to reach the site of tissue damage. Also, it has not been determined if circulating cells are equivalent to the multi-potent bone marrow stem cells, but preliminary data from our and other laboratories suggest that at a minimum, progenitors for many cell types reside in the blood. To begin to understand circulating stem cell biology we have focused on one type, namely circulating endothelial cell progenitors (CEPs), i.e, circulating cells that can differentiate into endothelial cells. Our first goal is to further the understanding of CEP biology by better delineating their phenotype(s) and identifying factors that control their growth and differentiation. This understanding may allow us to modulate CEP function in vivo to clinical advantage. Another component of stem cell biology about which little is known is how systemic disorders might alter their function. Our interest in particular is in how diabetes may affect CEP function. Evidence from our laboratory indicates that CEP dysfunction may be involved in diabetes associated vascular disease and that CEP therapy can improve vascularization in diabetic mice. Our second goal is to determine how the diabetic environment alters CEP function. To accomplish our goals we will 1) define the role of blood-derived CD34+ and CD14+ enriched cells in neovascularization in vivo; 2) identify molecular and cellular regulators of CEP growth and differentiation, and potential diabetes induced changes in these regulators in vivo; and 3) delineate potential roles of exogenous CEP modulators on CEP function in neovascularization in diabetic and non-diabetic mice.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
2R01DK055965-04A2
Application #
6683050
Study Section
Pathology A Study Section (PTHA)
Program Officer
Jones, Teresa L Z
Project Start
1998-09-30
Project End
2007-04-30
Budget Start
2003-06-15
Budget End
2004-04-30
Support Year
4
Fiscal Year
2003
Total Cost
$275,700
Indirect Cost
Name
University of Iowa
Department
Other Health Professions
Type
Schools of Arts and Sciences
DUNS #
062761671
City
Iowa City
State
IA
Country
United States
Zip Code
52242
Schatteman, Gina C; Awad, Ola; Nau, Eric et al. (2010) Lin- cells mediate tissue repair by regulating MCP-1/CCL-2. Am J Pathol 177:2002-10
Oberley, Christopher C; Gourronc, Francoise; Hakimi, Shinkai et al. (2008) Murine epidermal side population possesses unique angiogenic properties. Exp Cell Res 314:720-8
Schatteman, Gina C; Dunnwald, Martine; Jiao, Chunhua (2007) Biology of bone marrow-derived endothelial cell precursors. Am J Physiol Heart Circ Physiol 292:H1-18
Awad, Ola; Dedkov, Eduard I; Jiao, Chunhua et al. (2006) Differential healing activities of CD34+ and CD14+ endothelial cell progenitors. Arterioscler Thromb Vasc Biol 26:758-64
Awad, Ola; Jiao, Chunhua; Ma, Ning et al. (2005) Obese diabetic mouse environment differentially affects primitive and monocytic endothelial cell progenitors. Stem Cells 23:575-83
Schatteman, Gina C (2004) Adult bone marrow-derived hemangioblasts, endothelial cell progenitors, and EPCs. Curr Top Dev Biol 64:141-80
Schatteman, Gina C; Awad, Ola (2004) Hemangioblasts, angioblasts, and adult endothelial cell progenitors. Anat Rec A Discov Mol Cell Evol Biol 276:13-21
Wang, Chunlin; Jiao, Chunhua; Hanlon, Heather D et al. (2004) Mechanical, cellular, and molecular factors interact to modulate circulating endothelial cell progenitors. Am J Physiol Heart Circ Physiol 286:H1985-93
Schatteman, Gina C (2004) Non-classical mechanisms of heart repair. Mol Cell Biochem 264:103-17
Jiao, Chunhua; Bronner, Sarah; Mercer, Keri L N et al. (2004) Epidermal cells accelerate the restoration of the blood flow in diabetic ischemic limbs. J Cell Sci 117:1055-63

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