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Ann Thorac Surg 2007;83:1499-1500
© 2007 The Society of Thoracic Surgeons

Original Articles: Cardiovascular

Invited commentary

Yao Liang Tang, MD, PhD, Michael Ian Phillips, PhD, Dsc, FAHA

Stem Cell Biology, Keck Graduate Institute, 535 Watson Dr, Claremont, CA 91711

(Email: ytang{at}kgi.edu; ian_phillips{at}kgi.edu).

Heart failure due to acute myocardial infarction is a growing worldwide problem [1]. Cellular therapy with stem cells is a promising new approach for reversing left ventricular remodeling in ischemic heart disease. Regenerative medicine in cardiology is a new field based on the possibility of replacing lost cardiac cells and improving the function of injured hearts by cell transplantation. Adult cardiac tissue has limited regenerative capacity, although resident cardiac stem cells were recently discovered in the adult heart [2, 3]. However, the resident cardiac stem cells are in such low numbers, even though they can self-renew and regenerate the myocardium, myocardial damage is usually irreversible. An ischemic myocardium is also a lethal environment for stem cell multiplication. Therefore, for cell therapy it is necessary to find an abundant source of stem cells from noncardiac sources to apply to heart repair. Several sources of autologous stem cells, such as bone marrow-derived mesenchymal stem cells [4–6], skeletal myoblast [7], adipose derived mesenchymal stem cells [8], and hematopoietic stem cells [9] have been tested as cellular therapy for myocardial infarction. This innovative strategy of autologous transplantation is limited in elderly patients whose supply of autologous stem cells from these sources diminishes with age [10] or is dysfunctional with chronic disease [11]. Umbilical cord blood cells (UCBC) have been previously explored for myocardial tissue repair [12]. In this issue, a study by Wu and colleagues [13] describes a new source of stem cells named human umbilical cord derived stem cells (UCDS), which can be isolated from the fresh human umbilical cord through enzymatic digestion. Unlike UCBC, UCDS cells are negative for CD34 and CD45, the marker for UCBC [14] and hematopoietic stem cells [15], but highly express markers for adhesion molecules. Wu and colleagues [13] investigated the potential of UCDS cells to improve cardiac function after myocardial infarction and found that UCDS have several advantages. First, UCDS are multi-potent cell lines. They differentiate into three normal cell components of the heart: (1) cardiomyocytes, (2) endothelial cells, and (3) smooth muscle cells after intramyocardial implantation in vivo. Second, engrafted UCDS cells produce important paracrine factors, including VEGF. It has been recognized that part of the action of engrafted stem cells is a paracrine effect. In grafted bone marrow derived MSCs, paracrine release plays a key role in inhibiting apoptosis of ischemic myocardium [4]. Wu and colleagues [13] showed that the delivery of UCDS into the injured heart of young rats resulted in improved left ventricular function 1 month after myocardial infarction. However, it is important to note that they did not study the situation of long-term cell survival. Cell survival is a critical problem for allogeneic cell transplantation. In theory, as a source of young healthy stem cells, UCDS cells can be frozen and stored from birth and made available for autologous transplantation to the same patient several decades later, especially elderly myocardial infarcted patients with chronic diseases, such as diabetes. Attractive as the idea is, the test of banking UCDS cells for future cardiovascular regeneration is many years away.


   Acknowledgments
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 Acknowledgments
References
 
Dr Tang is supported by the American Heart Association (grant no. 0325378B) and the New Research Grant from the University of South Florida. Dr Phillips is supported by grants from the National Institutes of Health (grant no. HL77602, grant no. MERIT HL27339).


   References
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 Acknowledgments
 References
 

  1. Braunwald E, Bristow MR. Congestive heart failure: fifty years of progress Circulation 2000;102:IV14-IV23.[Medline]
  2. Beltrami AP, Barlucchi L, Torella D, et al. Adult cardiac stem cells are multipotent and support myocardial regeneration Cell 2003;114:763-776.[Medline]
  3. Oh H, Bradfute SB, Gallardo TD, et al. Cardiac progenitor cells from adult myocardium: homing, differentiation, and fusion after infarction Proc Natl Acad Sci U S A 2003;100:12313-12318.[Abstract/Free Full Text]
  4. Tang YL, Zhao Q, Zhang YC, et al. Autologous mesenchymal stem cell transplantation induce VEGF and neovascularization in ischemic myocardium Regul Pept 2004;117:3-10.[Medline]
  5. Tang YL, Tang Y, Zhang YC, Qian K, Shen L, Phillips MI. Improved graft mesenchymal stem cell survival in ischemic heart with a hypoxia-regulated heme oxygenase-1 vector J Am Coll Cardiol 2005;46:1339-1350.[Abstract/Free Full Text]
  6. Tang YL, Zhao Q, Qin X, Shen L, Cheng L, Ge J, Phillips MI. Paracrine action enhances the effects of autologous mesenchymal stem cell transplantation on vascular regeneration in rat model of myocardial infarction Ann Thorac Surg 2005;80:229-236.[Abstract/Free Full Text]
  7. Tang YL. Cellular therapy with autologous skeletal myoblasts for ischemic heart disease and heart failure Methods Mol Med 2005;112:193-204.[Medline]
  8. Yamada Y, Wang XD, Yokoyama S, Fukuda N, Takakura N. Cardiac progenitor cells in brown adipose tissue repaired damaged myocardium Biochem Biophys Res Commun 2006;342:662-670.[Medline]
  9. Orlic D, Hill JM, Arai AE. Stem cells for myocardial regeneration Circ Res 2002;91:1092-1102.[Abstract/Free Full Text]
  10. Anversa P, Rota M, Urbanek K, et al. Myocardial aging—a stem cell problem Basic Res Cardiol 2005;100:482-493.[Medline]
  11. Rota M, LeCapitaine N, Hosoda T, et al. Diabetes promotes cardiac stem cell aging and heart failure, which are prevented by deletion of the p66shc gene Circ Res 2006;99:42-52.[Abstract/Free Full Text]
  12. Friedrich EB, Bohm M. Human umbilical cord blood cells and myocardial infarction: novel ways to treat an old problem Cardiovasc Res 2005;66:4-6.[Free Full Text]
  13. Wu KH, Zhou B, Yu CT, et al. Therapeutic potential of human umbilical cord derived stem cells in a rat myocardial infarction model Ann Thorac Surg 2007;83:1491-1500.[Abstract/Free Full Text]
  14. Hirata Y, Sata M, Motomura N, et al. Human umbilical cord blood cells improve cardiac function after myocardial infarction Biochem Biophys Res Commun 2005;327:609-614.[Medline]
  15. Balsam LB, Wagers AJ, Christensen JL, Kofidis T, Weissman IL, Robbins RC. Haematopoietic stem cells adopt mature haematopoietic fates in ischaemic myocardium Nature 2004;428:668-673.[Medline]

Related Article

Therapeutic Potential of Human Umbilical Cord Derived Stem Cells in a Rat Myocardial Infarction Model
Kai Hong Wu, Bin Zhou, Cun Tao Yu, Bin Cui, Shi Hong Lu, Zhong Chao Han, and Ying Long Liu
Ann. Thorac. Surg. 2007 83: 1491-1498. [Abstract] [Full Text] [PDF]




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