This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Dimmeler, S. Articles by Leri, A. Search for Related Content PubMed PubMed Citation Articles by Dimmeler, S. Articles by Leri, A. Related Collections ACE/Angiotension receptors Angiogenesis Other diabetes Other Treatment Acute myocardial infarction

(Circulation Research. 2008;102:1319.)
© 2008 American Heart Association, Inc.

Reviews

Aging and Disease as Modifiers of Efficacy of Cell Therapy

Stefanie Dimmeler, Annarosa Leri

From Molecular Cardiology, Department of Internal Medicine III (S.D.), University of Frankfurt, Germany; and the Departments of Anesthesia and Medicine (A.L.), Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass.

Correspondence to Stefanie Dimmeler, PhD, Molecular Cardiology, Department of Internal Medicine III, University of Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany. E-mail Dimmeler{at}em.uni-frankfurt.de

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

The Stem Cell Movement [2008;102:1155–1168]

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 therapy is a promising option for treating ischemic diseases and heart failure. Adult stem and progenitor cells from various sources have experimentally been shown to augment the functional recovery after ischemia, and clinical trials have confirmed that autologous cell therapy using bone marrow—derived or circulating blood–derived progenitor cells is safe and provides beneficial effects. However, aging and risk factors for coronary artery disease affect the functional activity of the endogenous stem/progenitor cell pools, thereby at least partially limiting the therapeutic potential of the applied cells. In addition, age and disease affect the tissue environment, in which the cells are infused or injected. The present review article will summarize current evidence for cell impairment during aging and disease but also discuss novel approaches how to reverse the dysfunction of cells or to refresh the target tissue. Pretreatment of cells or the target tissue by small molecules, polymers, growth factors, or a combination thereof may provide useful approaches for enhancement of cell therapy for cardiovascular diseases.

Key Words: angiogenesis • diabetes • stem cells

This article has been cited by other articles:

				P. Spallarossa, P. Altieri, C. Aloi, S. Garibaldi, C. Barisione, G. Ghigliotti, G. Fugazza, A. Barsotti, and C. Brunelli Doxorubicin induces senescence or apoptosis in rat neonatal cardiomyocytes by regulating the expression levels of the telomere binding factors 1 and 2 Am J Physiol Heart Circ Physiol, December 1, 2009; 297(6): H2169 - H2181. [Abstract] [Full Text] [PDF]

				J. Ferreira-Martins, C. Rondon-Clavo, D. Tugal, J. A. Korn, R. Rizzi, M. E. Padin-Iruegas, S. Ottolenghi, A. De Angelis, K. Urbanek, N. Ide-Iwata, et al. Spontaneous Calcium Oscillations Regulate Human Cardiac Progenitor Cell Growth Circ. Res., October 9, 2009; 105(8): 764 - 774. [Abstract] [Full Text] [PDF]

				B. J. Gersh, R. D. Simari, A. Behfar, C. M. Terzic, and A. Terzic Cardiac Cell Repair Therapy: A Clinical Perspective Mayo Clin. Proc., October 1, 2009; 84(10): 876 - 892. [Abstract] [Full Text] [PDF]

				J. P. Singh Enabling Technologies for Homing and Engraftment of Cells for Therapeutic Applications J. Am. Coll. Cardiol. Intv., August 1, 2009; 2(8): 803 - 804. [Full Text] [PDF]

				K. R. Sipido, A. Tedgui, S. D. Kristensen, G. Pasterkamp, H. Schunkert, M. Wehling, P. G. Steg, W. Eisert, F. Rademakers, B. Casadei, et al. Identifying needs and opportunities for advancing translational research in cardiovascular disease Cardiovasc Res, August 1, 2009; 83(3): 425 - 435. [Full Text] [PDF]

				D. Cesselli, A. P. Beltrami, S. Rigo, N. Bergamin, F. D'Aurizio, R. Verardo, S. Piazza, E. Klaric, R. Fanin, B. Toffoletto, et al. Multipotent Progenitor Cells Are Present in Human Peripheral Blood Circ. Res., May 22, 2009; 104(10): 1225 - 1234. [Abstract] [Full Text] [PDF]

				D. P Sieveking and M. K. Ng Cell therapies for therapeutic angiogenesis: back to the bench Vascular Medicine, May 1, 2009; 14(2): 153 - 166. [Abstract] [PDF]

				G. Suzuki, V. Iyer, T. Cimato, and J. M. Canty Jr Pravastatin Improves Function in Hibernating Myocardium by Mobilizing CD133+ and cKit+ Bone Marrow Progenitor Cells and Promoting Myocytes to Reenter the Growth Phase of the Cardiac Cell Cycle Circ. Res., January 30, 2009; 104(2): 255 - 264. [Abstract] [Full Text] [PDF]

				S. Dimmeler and M. Tjwa Better Regenerative Output After Cellular Input: Healing Hearts by Combining Basic Fibroblast Factor and Cell-Based Therapy J. Am. Coll. Cardiol., December 2, 2008; 52(23): 1866 - 1868. [Full Text] [PDF]

				M. Rota, M. E. Padin-Iruegas, Y. Misao, A. De Angelis, S. Maestroni, J. Ferreira-Martins, E. Fiumana, R. Rastaldo, M. L. Arcarese, T. S. Mitchell, et al. Local Activation or Implantation of Cardiac Progenitor Cells Rescues Scarred Infarcted Myocardium Improving Cardiac Function Circ. Res., July 3, 2008; 103(1): 107 - 116. [Abstract] [Full Text] [PDF]