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International Journal of Sports and Exercise Medicine





DOI: 10.23937/2469-5718/1510008



Exercise and Stem Cell Therapeutics for the Infarcted Heart

Joseph R Libonati*


Director Laboratory of Innovative and Translational Nursing Research, School of Nursing, University of Pennsylvania, USA


*Corresponding author: Joseph R. Libonati, Director Laboratory of Innovative and Translational Nursing Research, School of Nursing, University of Pennsylvania, 126B Claire M. Fagin Hall, 418 Curie Boulevard, Philadelphia, PA 19104-4217, USA, Tel: 215-746-3986, E-mail: jlibonat@nursing.upenn.edu
Int J Sports Exerc Med, IJSEM-1-008, (Volume 1, Issue 2), Commentary; ISSN: 2469-5718
Received: April 15, 2015 | Accepted: May 15, 2015 | Published: May 18, 2015
Citation: Libonati JR (2015) Exercise and Stem Cell Therapeutics for the Infarcted Heart. Int J Sports Exerc Med 1:008. 10.23937/2469-5718/1510008
Copyright: © 2015 Libonati JR. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.



Heart failure afflicts 5.1 million individuals in the United States and its prevalence is expected to increase 25% by 2030. It is associated with a poor quality of life, increased mortality, and is extremely expensive to health care systems [1-4]. The progressive loss of cardiomyocytes is a central feature of heart failure from multiple etiologies. Thus there is a dire need for interventions that can preserve or even increase the number of well-functioning cardiac myocytes in patients with heart failure [5].

In this regard, the field of stem cell therapeutics has provided some very significant findings over the last fifteen or so years [5]. The field was initiated by attempts to utilize skeletal myoblasts to repopulate the damaged heart [6]. Since that time, numerous preclinical and clinical studies have been conducted (For Review See 5). Numerous studies have injected or infused a wide variety of stem cell sub-types in the heart [5]. While there is great controversy regarding the physiological mechanisms of improvement and the best stem cell type/number to use; the general findings of these studies suggest that stem cell therapy can benefit myocardial function and attenuate infarct size in both experimental animals and patients [5].

Still, despite these promising results, further advances are needed to more fully realize the benefits of stem cell therapy. One intervention that might prove to be a beneficial adjuvant is aerobic exercise. Beyond being safe and low cost, aerobic exercise changes the overall metabolic milieu of the heart and may trigger reparative mechanisms integral for success in stem cell therapeutics. For example, low engraftment and long term retention of stem cells have limited the overall efficacy of cell therapy [5]. By increasing cardiac output and stimulating a host of inflammatory and cell adhesion processes, aerobic exercise may increase stem cell homing and retention in the heart [7].

Studies have shown that the heart contains a population of progenitor cells that can form new cardiac tissue, albeit at very low rates [8]. Thus, while most cardiac myocytes in the adult heart are terminally differentiated, some new cardiac myocytes and endothelial cells can be formed from endogenous sources [8]. It is well accepted that stem cells initiate growth factor paracrine signaling to host myocardium, and it is feasible that stem cell paracrine signaling is altered by exercise, which in its own right, activates insulin-like growth factor signaling and is seminal in the development of physiologic-induced cardiac hypertrophy following exercise training [9]. Moreover aerobic exercise training may alter this dynamic, as training has been reported to increase the myocardial abundance of endogenous stem cells (c-Kit+ cells), increase the rate of cardiac myocyte proliferation, and attenuate cardiomyocyte cell death [10-12]. Additionally, other studies have shown that aerobic exercise stimulates the mobilization and circulation of endogenous progenitors [13,14].

To date only one small study has examined the effect of bone marrow mononuclear cells transplantation in a rat model of myocardial infarction following thirty days of low level swimming exercise (15 min/day; 3 days/wk). The authors found an improvement in left ventricular ejection fraction and more favorable post infarction remodeling following swim training compared to sedentary animals receiving cell injections alone [15]. Thus while stem cell therapeutics holds great promise for treating heart failure, novel adjuvant therapies like aerobic exercise may potentially optimize treatment efficacy. While understanding how exercise alters stem cell biology is in its infant stages, the use of therapies like cardiac rehabilitation may have utility far beyond what was previously understood. While accessing funding for such studies is challenging, the preliminary biology is enticing for a call to action in understanding whether exercise may improve the efficacy of stem cell therapeutics.


Acknowledgements

This work was supported by NHLBI 1R21HL11377.


References
  1. Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, et al. (2014) Executive summary: heart disease and stroke statistics-2014 update: a report from the American Heart Association. Circulation 129: 399-410.

  2. Kochanek KD, Xu JQ, Murphy SL, Minino AM, Kung HC (2011) Deaths: final data for 2009. National Vital Statistics Reports 60: 1-117.

  3. Heidenriech PA, Trogdon JG, Khavjou OA, Butler J, Dracup K, et al. (2011) Forecasting the future of cardiovascular disease in the United States: A policy statement from the American Heart Association. Circulation 123: 933-944.

  4. Wang G Zhang Z, Ayala C, Wall HK, Fang J (2010) Costs of heart failure-related hospitalizations in patients aged 18 to 64 years. Am J Manag Care 16: 769-776.

  5. Sanganalmath SK1, Bolli R (2013) Cell therapy for heart failure: a comprehensive overview of experimental and clinical studies, current challenges, and future directions. Circ Res 113: 810-834.

  6. Taylor DA, Atkins BZ, Hungspreugs P, Jones TR, Reedy MC, et al. (1998) Regenerating functional myocardium: improved performance after skeletal myoblast transplantation. Nat Med 4: 929-933.

  7. Libonati JR, Zaslavsky A, Blanco E, Garcia V, Elser J, et al. (2011) Exercise increases myocardial retention of exogenously infused bone marrow-derived cells. International Society for Heart Failure Research, (Abstract 136), Philadelphia, PA, USA.

  8. van Berlo JH, Kanisicak O, Maillet M, Vagnozzi RJ, Karch J, et al. (2014) c-kit+ cells minimally contribute cardiomyocytes to the heart. Nature 509: 337-341.

  9. McMullen JR, Shioi T, Zhang L, Tarnavski O, Sherwood MC, et al. (2003) Phosphoinositide 3-kinase (p110alpha) plays a critical role for the induction of physiological, but not pathological, cardiac hypertrophy. Proc Natl Acad Sci U S A 100: 12355-12360.

  10. Kolwicz SC, MacDonnell SM, Renna BF, Reger PO, Seqqat R, et al. (2009) Left ventricular remodeling with exercise in hypertension. Am J Physiol Heart Circ Physiol 297: H1361-1368.

  11. Bostr?m P, Mann N, Wu J, Quintero PA, Plovie ER, et al. (2010) C/EBPß controls exercise-induced cardiac growth and protects against pathological cardiac remodeling. Cell 143: 1072-1083.

  12. Waring CD, Vicinanza C, Papalamprou A, Smith AJ, Purushothaman S, et al. (2014) The adult heart responds to increased workload with physiologic hypertrophy, cardiac stem cell activation, and new myocyte formation. Eur Heart J 35: 2722-2731.

  13. Brehm M, Picard F, Ebner P, Turan G, B?lke E, et al. (2009) Effects of exercise training on mobilization and functional activity of blood-derived progenitor cells in patients with acute myocardial infarction. Eur J Med Res 14: 393-405.

  14. Rehman J, Li J, Parvathaneni L, Karlsson G, Panchal VR, et al. (2004) Exercise acutely increases circulating endothelial progenitor cells and monocyte-/macrophage-derived angiogenic cells. J Am Coll Cardiol 43: 2314-2318.

  15. Cosmo S, Francisco JC, Cunha RC, Macedo RM, Faria-Neto JR, et al. (2012) Effect of exercise associated with stem cell transplantation on ventricular function in rats after acute myocardial infarction. Rev Bras Cir Cardiovasc 27: 542-551.


Special issue title: Sports Medicine and Exercise Physiology

Handling Editor: Chad A Krueger

Executive chief resident

Orthopaedic Surgery Resident

San Antonio Military Medical Center

USA



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