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. [unreadable] [unreadable]