Assesment of cardioprotection provided by intramyocardial or subcutaneous transplantation of human adipose stem cells overexpressing HMOX-1

Stem cells are currently explored as therapy against heart failure. However, several unsolved issues still remain, namely the survival of cells post-transplantation, the role of local environmental conditions on the fate of transplanted cells, or mechanis ms by which stem cells improve cardiac function.To improve the survival and integration of stem cells into the ischemic myocardium, various strategies have been developed, including genetic modifications of the cells to overexpress specific factors. The r esearch group in Oslo for which it is applied to join has previously shown that the delivery of DNA encoding for heme oxygenase (HMOX)-1 into skeletal muscle had beneficial effects for heart cells ex vivo, in vitro, and in vivo. The aim of this project is to evaluate if adipose-derived mesenchymal stem cells (ASCs) genetically modified to overexpress HMOX-1 induce cardioprotective effect when transplanted into mice. Two working hypothesis were outlined, namely that transplantation of stem cells overexpres sing HMOX-1 is more beneficial for the ischemic heart than delivery of "naive" stem cells, and that delivery of stem cells overexpressing HMOX-1 into a peripheral organ have the same efficiency for cardiac protection as intracardiac delivery, but less in vasive. Therefore, the local and subcutaneous transplantation of stem cells are to be compared in this project. The objectives are: (i) isolation of ASCs from human adipose tissue and modification to overexpress HMOX-1; (ii) assessment the fate of ASCs a fter intramyocardial or subcutaneous transplantation, by following their engraftment and survival into the host tissue; (iii) evaluation of cardioprotective effects of ASCs overexpressing HMOX-1 ex vivo in the ischemic isolated mouse heart. The main scie ntific benefit of this project may be the elaboration of a remote cell-based therapy for myocardial infarction, as an alternative treatment for human cardiac disease.