Most of the work performed on bone marrow-derived progenitor cells (BMPCs) to date has investigated their differentiation under chemical stimuli, but in vivo environments may not provide these cytokines in levels used to elicit the desired response. Instead, BMPCs might rely on in vivo mechanical signals for maintenance of their phenotype. Based on the applicant's preliminary data, the goal of this project is to determine the differentiation potential of rat BMPCs towards vascular cells under three physiologically relevant mechanical stimuli; namely, shear stress, cyclic stretch, and cyclic hydrostatic pressure. To that end, we propose two specific aims: (1) To elucidate the dose-dependent response of BMPCs to varying magnitudes and frequencies of each separate mechanical force stimulus; i.e., shear stress, cyclic stretch, and cyclic hydrostatic pressure. (2) To elucidate the temporal response of BMPCs to the most appropriate frequency and magnitude determined from Specific Aim 1 for each mechanical force stimulus. The endpoints that will be evaluated are vascular smooth muscle cell- and endothelial cell-specific protein expression, functional indicators for both of these cell types, cell viability, and basic morphology. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31EB004791-02
Application #
6954172
Study Section
Special Emphasis Panel (ZRG1-DIG-B (21))
Program Officer
Khachaturian, Henry
Project Start
2004-09-30
Project End
2007-08-31
Budget Start
2005-09-01
Budget End
2006-08-31
Support Year
2
Fiscal Year
2005
Total Cost
$34,047
Indirect Cost
Name
University of Pittsburgh
Department
Surgery
Type
Schools of Medicine
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Maul, Timothy M; Hamilton, Douglas W; Nieponice, Alejandro et al. (2007) A new experimental system for the extended application of cyclic hydrostatic pressure to cell culture. J Biomech Eng 129:110-6
Nieponice, Alejandro; Maul, Timothy M; Cumer, Joy M et al. (2007) Mechanical stimulation induces morphological and phenotypic changes in bone marrow-derived progenitor cells within a three-dimensional fibrin matrix. J Biomed Mater Res A 81:523-30