The field of cardiac regeneration using stem cells has the potential to revolutionize the treatment of heart failure. Several stem cells e.g. human mesenchymal stem cells (hMSCs) and human cardiosphere-derived cells (hCDCs) are currently in clinical trials. However, irrespective of the cell type, timing/mode of transplantation, functional benefits have been modest at best. One important cause of low functional benefit is low levels of acute retention (24 hrs following transplantation) and long term engraftment. If we could increase the number of cells that survive and induce them to proliferate in vivo, we would be able to greatly increase cardiac repair. In order to accomplish this, a comprehensive understanding of the determinants of cell survival and proliferation are needed.A steady supply of nutrients/substrates and specific cues from the environment are universal requirements for cell survival and proliferation. Our preliminary results in CDCs and MSCs indicate that these cells have a 'unique metabolic signature'. However, the regulators of this metabolic signature are not known. The premise of the proposed studies is that maintenance of cellular metabolism following transplantation will permit cell survival and multiplication, resulting in enhanced cardiac repair following transplantation.In this grant, we propose a comprehensive evaluation of metabolism and its regulators in cardiosphere-derived cells (CDCs). We have designed novel, bio-degradable scaffolds comprised of serum and hyaluronic acid that adhere to beating myocardium, encapsulate stem cells and provide them with an environment that promotes cell survival and multiplication. The effects of encapsulating cells on myocardial repair will be investigated using molecular imaging.We anticipate that our results will be applicable to other adult stem cells and cells derived from induced pluripotent stem cells and will boost cardiac regeneration.
|Effective start/end date||07/01/2014 → 06/30/2016|