Mesenchymal stem cells modified with Akt prevent remodeling and restore performance of infarcted hearts.

Journal Article

Transplantation of adult bone marrow-derived mesenchymal stem cells has been proposed as a strategy for cardiac repair following myocardial damage. However, poor cell viability associated with transplantation has limited the reparative capacity of these cells in vivo. In this study, we genetically engineered rat mesenchymal stem cells using ex vivo retroviral transduction to overexpress the prosurvival gene Akt1 (encoding the Akt protein). Transplantation of 5 x 10(6) cells overexpressing Akt into the ischemic rat myocardium inhibited the process of cardiac remodeling by reducing intramyocardial inflammation, collagen deposition and cardiac myocyte hypertrophy, regenerated 80-90% of lost myocardial volume, and completely normalized systolic and diastolic cardiac function. These observed effects were dose (cell number) dependent. Mesenchymal stem cells transduced with Akt1 restored fourfold greater myocardial volume than equal numbers of cells transduced with the reporter gene lacZ. Thus, mesenchymal stem cells genetically enhanced with Akt1 can repair infarcted myocardium, prevent remodeling and nearly normalize cardiac performance.

Full Text

Duke Authors

Cited Authors

  • Mangi, AA; Noiseux, N; Kong, D; He, H; Rezvani, M; Ingwall, JS; Dzau, VJ

Published Date

  • September 2003

Published In

Volume / Issue

  • 9 / 9

Start / End Page

  • 1195 - 1201

PubMed ID

  • 12910262

International Standard Serial Number (ISSN)

  • 1078-8956

Digital Object Identifier (DOI)

  • 10.1038/nm912

Language

  • eng

Conference Location

  • United States