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(Circulation Research. 2008;102:1471.)
© 2008 American Heart Association, Inc.

Reviews

Genetic Enhancement of Stem Cell Engraftment, Survival, and Efficacy

Marc S. Penn, Abeel A. Mangi

From the Skirball Laboratory for Cardiovascular Cellular Therapeutics (M.S.P.), Center for Cardiovascular Cell Therapy, Heart and Vascular Institute, Departments of Cardiovascular Medicine and Stem Cell Biology and Regenerative Medicine, and the Department of Thoracic and Cardiovascular Surgery (A.A.M.), Cleveland Clinic, Cleveland, Ohio.

Correspondence to Marc S. Penn, MD, PhD, Director, Skirball Laboratory for Cardiovascular Cellular Therapeutics, Center for Cardiovascular Cellular Therapeutics, NE3, 9500 Euclid Avenue, Cleveland, OH 44195. E-mail pennm{at}ccf.org

This Review is part of a thematic series on Cellular Therapy, which includes the following articles:

The Stem Cell Movement

Aging and Disease as Modifiers of Efficacy of Cell Therapy

Genetic Enhancement of Stem Cell Engraftment, Survival, and Efficacy

Paracrine Signaling in Cell Transplantation

Assessment and Optimization of Cell Engraftment After Transplantation

Immune Biology of Stem Cells

Cardiogenic Differentiation and Transdifferentiation of Stem Cells

Stem Cell Homing to Sites of Injury

Regulatory Considerations in Cell Transplantation
Eduardo Marbán Editor

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.

Key Words: gene transfer • myocardial repair • stem cells • heart failure • acute myocardial infarction

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