Approximately 1.1 million Americans suffer from an acute myocardial infarction each year. The limited self-regeneration capacity of the adult heart is such that the original injury frequently leads to progressive disease and ultimately heart failure. Recently a number of biological therapies using angiogenic growth factors, endothelial progenitor cells (EPCs), and cells with the capacity to regenerate damaged myocardial tissue have been applied in preclinical and clinical studies. One barrier to this approach has been the relatively limited supply of autologous stem and progenitor cells that can be obtained with clinically acceptable morbidity from cell sources such as skeletal muscle and bone marrow. Researchers from this group have recently described adipose tissue as a potential alternate cell source. We have published studies showing that adipose tissue is a rich source of cells with properties similar to those of marrow-derived mesenchymal stem cells (MSCs) and here present data showing that it also contains EPCs and cells expressing angiogenic growth factors. Suction-assisted lipoplasty (liposuction) is a common procedure allowing rapid collection of relatively large amounts of human tissue with low morbidity. Thus, we hypothesize that adipose tissue represents a clinically relevant source of cells for myocardial therapy. In this study we will use a mouse occlusion/reperfusion myocardial infarct model to examine the ability of adipose tissue-derived cells to engraft damaged myocardium and to differentiate in vivo into endothelial and cardiomyocytic cells. Donor cells will be obtained from the Rosa 26 transgenic mouse strain in which the lacZ transgene is expressed in virtually every tissue. This will allow histologic detection of donor-derived cells in a normal (lacZ-negative) recipient background. This proof-of-concept, Phase I SBIR study will evaluate the role of timing of cell administration the route of cell administration (direct injection vrs intravenous delivery), and the effects of cell culture on homing and engraftment. This information will improve our understanding of the potential role of adipose tissue-derived cells in myocardial therapy. Successful completion of these studies will lead to a Phase II project in which cell delivery variables will be optimized in the context of improvements in myocardial function.
Thesaurus Terms: adipose tissue, cardiovascular disorder therapy, cell transplantation, myocardial infarction, therapy design /development angiogenesis, apoptosis, cardiac myocyte, cell differentiation, intravenous administration, vascular endothelium clinical research, genetically modified animal, laboratory mouse, tissue /cell culture
