This proposal describes a two year career enhancement program of intensive training and hands-on experience in stem cell culture which will provide the basis for re-directing the Principal Investigator's ongoing research in transplantation to study the survival of human embryonic stem cell-derived cardiomyocytes after intracardiac injection into infarcted rat hearts. The proposed training program will provide an opportunity for the Principal Investigator to enter the field of stem cell biology under the direction of her mentors Dr. Gay Crooks and Dr. Robert Kloner. Dr. Crooks is a recognized leader in the field of stem cell research. She is Director of the Stem Cell Program and is a Professor of Pediatrics at Childrens Hospital Los Angeles and the University of Southern California. She is renowned in the field of hematopoiesis, well-respected for her contributions to the field of stem cell research and has trained numerous postdoctoral fellows and students in her laboratory. The proposed training program is further enhanced by the co-mentorship of Dr. Robert Kloner, Director of the Heart Institute at Good Samaritan Hospital and a leader in the field of cardiomyocyte regeneration. An advisory committee of renowned scientists will provide scientific guidance, and were selected for their expertise that directly relates to the research proposed in this application. The research proposed will address whether over-expression of a cytoprotective gene in mesenchymal stem cells will enhance the survival and function of co-transplanted cardiomyocytes. Early gene expression changes associated with apoptosis, inflammation, cytoprotective gene expression and angiogenesis in human cardiomyocytes transplanted into infarcted rat hearts will be identified.
The specific aims i nclude: 1) To assess hESC-derived cardiomyocyte survival and function following transplantation of human cardiomyocytes with and without co-transplantation of mesenchymal stem cells overexpressing HO-1 into infarcted rat hearts. The long-term survival of cardiomyocytes will be monitored by bioluminescent imaging and function will be monitored by hemodynamic measurements and LV angiograms and 2) To identify early gene expression changes in human cardiomyocytes transplanted into infarcted nude rat hearts. Laser capture microdissection and focused pathway arrays will be used to study gene expression changes in hESC derived cardiomyocytes. The proposed training in stem cell biology will form the foundation for the Pi's future plans to extend her research in transplantation tolerance to studying early immune response events after stem cell transplantation.
| Kearns-Jonker, Mary; Dai, Wangde; Gunthart, Mirja et al. (2012) Genetically Engineered Mesenchymal Stem Cells Influence Gene Expression in Donor Cardiomyocytes and the Recipient Heart. J Stem Cell Res Ther S1: |
