Cellular therapy is a strategy aimed at repairing, enhancing, and replacing the biological function of a damaged tissue or system by means of autologous or allogeneic cells. Until very recently, most work involving cellular therapy had involved either the replacement (rescue) of hematopoietic tissue following myeloablative doses of chemotherapy, or the use of immune cells as therapy for cancer. Recent advances in understanding of stem and progenitor cell biology, cell delivery methods, and a range of animal models of human disease have also paved the way for exploring novel cellular strategies to address non-malignant diseases of multiple organs and tissues, including ischemic limbs, poorly healing wounds, ischemic hearts, and several others. In developing this proposal, we have built upon the synergistic expertise of leaders in complementary areas of stem and progenitor cell biology, who have each played key roles in defining a strongly collaborative environment at Indiana University in basic understanding as well as translation of adult stem cell research for diseases focusing on both the hematopoietic and cardiovascular systems. The central themes of this proposal are: 1) Defining synergistic interactions among progenitor cells of distinct lineages;2) Evaluation of progenitor cell types with regard to mechanisms of defective tissue repair and regeneration in the context of aging and acquired disease;and 3) study of cells from each of the three selected lineages (hematopoietic, mesenchymal, and endothelial) from three readily available tissue sources that facilitate direct translation into human disease (cord blood;adipose tissue;and vascular structures including umbilical cord and saphenous veins). Each of these themes will be consistently pursued using cells that have routinely been well-defined and purified using multi-marker cell analysis tools and in vivo functional evaluation. These themes will be developed in 4 """"""""full scale"""""""" projects which will continue throughout the operational time of the Consortium, complemented by 2 """"""""small scale"""""""" pilot proposals which will be submitted for additional consideration as described in detail below.
