Cardiomyocytes in the adult mammal exhibit little if any capacity to undergo cell division. Consequently cardiomyocyte loss due to injury or disease is irreversible. The ability to utilize intracardiac grafting as a means to replace scarred, nonfunctional myocardium in a diseased heart with viable, functional cardiomyocytes would have significant therapeutic value. Preliminary experiments from this laboratory have established the feasibility of intracardiac grafting using a variety of cell types. These studies demonstrate that the myocardium can serve as a stable platform for cells which have been manipulated in vitro. In this application we propose to extend these findings in an effort to develop models which test the feasibility of utilizing intracardiac grafting to effect myocardial replacement. We propose five Specific Aim with the goal of developing models which test the feasibility of intracardiac grafting as a means to effect myocardial repair. They are: 1: Intracardiac grafting in the mouse heart with fetal ventricular cardiomyocytes derived from mice expressing a cytological """"""""tag"""""""" in the myocardium. 2: Intracardiac grafting in the mouse heart with cardiomyocytes derived from murine embryonic stem (ES) cells. 3: Intracardiac grafting in the mouse heart with genetically modified skeletal myoblasts. 4: Intracardiac grafting in the infarcted rat heart with fetal ventricular cardiomyocytes derived from mice expressing a cytological """"""""tag"""""""" in the myocardium. 5: Intracardiac grafting in the dystrophic canine heart using dystrophin expressing fetal cardiomyocytes. Together, the proposed experiments should enable us to ascertain the feasibility of employing intracardiac graftings as a means to repair damaged or diseased myocardium.
Specific Aims 4 and 5 have the advantag that functional analyses of graft-bearing canine hearts are readily accomplished using established in house methodologies.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL053505-04
Application #
2638036
Study Section
Cardiovascular and Pulmonary Research A Study Section (CVA)
Project Start
1995-01-01
Project End
1998-12-31
Budget Start
1998-01-01
Budget End
1998-12-31
Support Year
4
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Indiana University-Purdue University at Indianapolis
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
005436803
City
Indianapolis
State
IN
Country
United States
Zip Code
46202