Topobiology of Cellular Cardiomyoplasty

Our work is focused on cell based therapy for heart failure. The goal is to utilize autologous human stem (adult stromal bone marrow, i.e., mesenchymal) cells (hMSC) for the repair and /or regeneration of the damaged cardiac tissue. In particular, understanding the microenvironment-dependent (target niche) signals  that can induce transdifferentiation of hMSC to cardiac phenotype is of paramount importance. The Microarray-based gene expression profiling technology will enable us to identify the key (network of) genes that are activated by the various ex-vivo imposed (culture) conditions (ex. growth factors, ECM, mechanical/electrical "preconditioning"). Understanding the conditions /cues involved in controlling the plasticity of hMSC is a prerequisite for engineering functional (and large scale) cardiac tissue integration.

Homing Stem Cells for Cardiac Repair

When a blockage of the coronary artery occurs, cardiomyocytes become injured. This injury induces the release a variety of cytokines as well as chemokines into the circulation. Chemokines play a pivotal role in "pulling" endothelial progenitor cells from the bone marrow and directing them to areas of injury. We hypothesize that the injured cardiac cells serve as the signaling nidus, initiating the chemokine mediated chemotactic gradient; acting as a local homing signal directing these stem cells towards the infracted area.

The experimental protocols are designed to establish the presence and quantify the cytokines/chemokines in peripheral circulation in response to myocardial injury, and evaluate the corresponding numbers of stem cell in circulation. This information will benefit the growing field of cell-based therapy that is attempting to repair and restore the injured myocardium. This may provide a means by which autologous progenitor cells can be chemically guided to both prevent the progression of myocyte injury following infarction, as well as, a potential therapy for treating end stage heart failure. The identification and quantification of both cytokines and chemokines, may aid in the development of a new marker for myocyte injury, leading to new screening tools for the early diagnosis of myocardial infarction. In addition the knowledge gained by understanding the process by which endogenous stem cells home to an area of injury will allow for the development of new therapies for guiding the healing process not only in the heart, but in other organ systems as well.

 
 Back to Top