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Review
. 2008 Jun 20;102(12):1471-82.
doi: 10.1161/CIRCRESAHA.108.175174.

Genetic enhancement of stem cell engraftment, survival, and efficacy

Marc S Penn  1 , Abeel A Mangi
Affiliations
Review

Genetic enhancement of stem cell engraftment, survival, and efficacy

Marc S Penn et al. Circ Res. .

Abstract

Cell-based therapies for the prevention and treatment of cardiac dysfunction offer the potential to significantly modulate cardiac function and improve outcomes in patients with cardiovascular disease. To date several clinical studies have suggested the potential efficacy of several different stem cell types; however, the benefits seen in clinical trials have been inconsistent and modest. In parallel, preclinical studies have identified key events in the process of cell-based myocardial repair, including stem cell homing, engraftment, survival, paracrine factor release, and differentiation that need to be optimized to maximize cardiac repair and function. The inconsistent and modest benefits seen in clinical trials combined with the preclinical identification of mediators responsible for key events in cell-based cardiac repair offers the potential for cell-based therapy to advance to cell-based gene therapy in an attempt to optimize these key events in the hope of maximizing clinical benefit. Below we discuss potential key events in cardiac repair and the mediators of these events that could be of potential interest for genetic enhancement of stem cell-based cardiac repair.

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Figures

Figure 1
Figure 1
Proposed stages of the development of strategies for stem cell based myocardial preservation and repair of injured myocardial tissue.
Figure 2
Figure 2. Schematic representation of the steps involved in stem cell based treatment of injured myocardial tissue
The stages begin with circulating stem cells (block with white nuclei) in the blood vessel to migration of stem cells into the injured myocardial tissue. The process is completed with the release of paracrine factors into the injured myocardium and/or differentiation of the engrafted stem cells into cardiac myocytes.
Figure 3
Figure 3. Pathways of mesenchymal stem cell based myocardial repair
Mesenchymal stem cells are genetically modified to increase their survival in injured myocardium. This modification results in (a) an increase in mesenchymal stem cells in the infarcted myocardium with a subsequent increase in surviving cardiac myocytes in the infarct zone. (b) The improvement could also be due to the increased release of proteins from the genetically enhanced mesenchymal stem cells leading to an increase in cardiac myocyte survival in the absence of mesenchymal stem cell engraftment. By either mechanism there is greater cardiac myocyte survival compared to control mesenchymal stem cells (c).
Figure 4
Figure 4
Summary of potential targets for genetic enhancement of stem cells
See this image and copyright information in PMC

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