Stem Cell Reviews and Reports

, Volume 10, Issue 3, pp 389–398 | Cite as

Therapeutic Application of Adipose Derived Stem Cells in Acute Myocardial Infarction: Lessons from Animal Models

  • B. A. Naaijkens
  • A. van Dijk
  • O. Kamp
  • P. A. J. Krijnen
  • H. W. M. Niessen
  • L. J. M. Juffermans


The majority of patients survive an acute myocardial infarction (AMI). Their outcome is negatively influenced by post-AMI events, such as loss of viable cardiomyocytes due to a post-AMI inflammatory response, eventually resulting in heart failure and/or death. Recent pre-clinical animal studies indicate that mesenchymal stem cells derived from adipose tissue (ASC) are new promising candidates that may facilitate cardiovascular regeneration in the infarcted myocardium. In this review we have compared all animal studies in which ASC were used as a therapy post-AMI and have focused on aspects that might be important for future successful clinical application of ASC.


Adipose derived stem cells Acute myocardial infarction Animal models Cellular therapy 



Adipose derived stem cell


Acute myocardial infarction


Intravenous injection


Intracoronary injection


Intramyocardial injection


Mesenchymal stem cell


Bone marrow derived mesenchymal stem cell


Stromal vascular fraction


Left ventricular ejection fraction




Conflict of Interest

The authors indicate no potential conflicts of interest.


  1. 1.
    Shah, V. K., & Shalia, K. K. (2011). Stem cell therapy in acute myocardial infarction: a pot of gold or Pandora’s Box. Stem Cells International, 2011, 536758.PubMedCentralPubMedCrossRefGoogle Scholar
  2. 2.
    Kuraitis, D., Ruel, M., & Suuronen, E. J. (2011). Mesenchymal stem cells for cardiovascular regeneration. Cardiovascular Drugs and Therapy, 25(4), 349–362.PubMedCrossRefGoogle Scholar
  3. 3.
    Roger, V. L., Go, A. S., Lloyd-Jones, D. M., et al. (2012). Executive summary: heart disease and stroke statistics–2012 update: a report from the American Heart Association. Circulation, 125(1), 188–197.PubMedGoogle Scholar
  4. 4.
    Pfeffer, M. A., & Braunwald, E. (1990). Ventricular remodeling after myocardial infarction. Experimental observations and clinical implications. Circulation, 81(4), 1161–1172.PubMedCrossRefGoogle Scholar
  5. 5.
    Friedenstein, A. J., Deriglasova, U. F., Kulagina, N. N., et al. (1974). Precursors for fibroblasts in different populations of hematopoietic cells as detected by the in vitro colony assay method. Experimental Hematology, 2(2), 83–92.PubMedGoogle Scholar
  6. 6.
    Zuk, P. A., Zhu, M., Ashjian, P., et al. (2002). Human adipose tissue is a source of multipotent stem cells. Molecular Biology of the Cell, 13(12), 4279–4295.PubMedCentralPubMedCrossRefGoogle Scholar
  7. 7.
    Naaijkens, B. A., Niessen, H. W., Prins, H. J., et al. (2012). Human platelet lysate as a fetal bovine serum substitute improves human adipose-derived stromal cell culture for future cardiac repair applications. Cell and Tissue Research, 348(1), 119–130.PubMedCentralPubMedCrossRefGoogle Scholar
  8. 8.
    Boyle, A. J., McNiece, I. K., & Hare, J. M. (2010). Mesenchymal stem cell therapy for cardiac repair. Methods in Molecular Biology, 660, 65–84.PubMedCrossRefGoogle Scholar
  9. 9.
    Oswald, J., Boxberger, S., Jorgensen, B., et al. (2004). Mesenchymal stem cells can be differentiated into endothelial cells in vitro. Stem Cells, 22(3), 377–384.PubMedCrossRefGoogle Scholar
  10. 10.
    Pittenger, M. F., & Martin, B. J. (2004). Mesenchymal stem cells and their potential as cardiac therapeutics. Circulation Research, 95(1), 9–20.PubMedCrossRefGoogle Scholar
  11. 11.
    Psaltis, P. J., Zannettino, A. C., Worthley, S. G., & Gronthos, S. (2008). Concise review: mesenchymal stromal cells: potential for cardiovascular repair. Stem Cells, 26(9), 2201–2210.PubMedCrossRefGoogle Scholar
  12. 12.
    Katz, A. J., Tholpady, A., Tholpady, S. S., Shang, H., & Ogle, R. C. (2005). Cell surface and transcriptional characterization of human adipose-derived adherent stromal (hADAS) cells. Stem Cells, 23(3), 412–423.PubMedCrossRefGoogle Scholar
  13. 13.
    Nakagami, H., Morishita, R., Maeda, K., Kikuchi, Y., Ogihara, T., & Kaneda, Y. (2006). Adipose tissue-derived stromal cells as a novel option for regenerative cell therapy. Journal of Atherosclerosis and Thrombosis, 13(2), 77–81.PubMedCrossRefGoogle Scholar
  14. 14.
    Varma, M. J., Breuls, R. G., Schouten, T. E., et al. (2007). Phenotypical and functional characterization of freshly isolated adipose tissue-derived stem cells. Stem Cells and Development, 16(1), 91–104.PubMedCrossRefGoogle Scholar
  15. 15.
    Rasmussen, J. G., Frobert, O., Holst-Hansen, C., et al. (2012). Comparison of human adipose-derived stem cells and bone marrow-derived stem cells in a myocardial infarction model. Cell Transplantation (Epub ahead of print).Google Scholar
  16. 16.
    Paul, A., Srivastava, S., Chen, G., Shum-Tim, D., & Prakash, S. (2013). Functional assessment of adipose stem cells for xenotransplantation using myocardial infarction immunocompetent models: comparison with bone marrow stem cells. Cell Biochemistry and Biophysics, 67(2), 263–273.PubMedCrossRefGoogle Scholar
  17. 17.
    Yamada, Y., Wang, X. D., Yokoyama, S., Fukuda, N., & Takakura, N. (2006). Cardiac progenitor cells in brown adipose tissue repaired damaged myocardium. Biochemical and Biophysical Research Communications, 342(2), 662–670.PubMedCrossRefGoogle Scholar
  18. 18.
    Bayes-Genis, A., Soler-Botija, C., Farre, J., et al. (2010). Human progenitor cells derived from cardiac adipose tissue ameliorate myocardial infarction in rodents. Journal of Molecular and Cellular Cardiology, 49(5), 771–780.PubMedCrossRefGoogle Scholar
  19. 19.
    Bai, X., Yan, Y., Song, Y. H., et al. (2010). Both cultured and freshly isolated adipose tissue-derived stem cells enhance cardiac function after acute myocardial infarction. European Heart Journal, 31(4), 489–501.PubMedCrossRefGoogle Scholar
  20. 20.
    Gaebel, R., Furlani, D., Sorg, H., et al. (2011). Cell origin of human mesenchymal stem cells determines a different healing performance in cardiac regeneration. PLoS One, 6(2), e15652.PubMedCentralPubMedCrossRefGoogle Scholar
  21. 21.
    Li, T. S., Cheng, K., Malliaras, K., et al. (2012). Direct comparison of different stem cell types and subpopulations reveals superior paracrine potency and myocardial repair efficacy with cardiosphere-derived cells. Journal of the American College of Cardiology, 59(10), 942–953.PubMedCentralPubMedCrossRefGoogle Scholar
  22. 22.
    Kim, S. W., Lee, D. W., Yu, L. H., et al. (2012). Mesenchymal stem cells overexpressing GCP-2 improve cardiac function through enhanced angiogenic properties in a myocardial infarction model. Cardiovascular Research, 95(4), 495–506.PubMedCrossRefGoogle Scholar
  23. 23.
    Cai, L., Johnstone, B. H., Cook, T. G., et al. (2009). IFATS collection: human adipose tissue-derived stem cells induce angiogenesis and nerve sprouting following myocardial infarction, in conjunction with potent preservation of cardiac function. Stem Cells, 27(1), 230–237.PubMedCentralPubMedCrossRefGoogle Scholar
  24. 24.
    Ii, M., Horii, M., Yokoyama, A., et al. (2011). Synergistic effect of adipose-derived stem cell therapy and bone marrow progenitor recruitment in ischemic heart. Laboratory Investigation, 91(4), 539–552.PubMedCrossRefGoogle Scholar
  25. 25.
    Hong, S. J., Kihlken, J., Choi, S. C., March, K. L., & Lim, D. S. (2013). Intramyocardial transplantation of human adipose-derived stromal cell and endothelial progenitor cell mixture was not superior to individual cell type transplantation in improving left ventricular function in rats with myocardial infarction. International Journal of Cardiology, 164(2), 205–211.PubMedCrossRefGoogle Scholar
  26. 26.
    Beitnes, J. O., Oie, E., Shahdadfar, A., et al. (2012). Intramyocardial injections of human mesenchymal stem cells following acute myocardial infarction modulate scar formation and improve left ventricular function. Cell Transplantation, 21(8), 1697–1709.CrossRefGoogle Scholar
  27. 27.
    van der Bogt, K. E., Schrepfer, S., Yu, J., et al. (2009). Comparison of transplantation of adipose tissue- and bone marrow-derived mesenchymal stem cells in the infarcted heart. Transplantation, 87(5), 642–652.PubMedCentralPubMedCrossRefGoogle Scholar
  28. 28.
    Leobon, B., Roncalli, J., Joffre, C., et al. (2009). Adipose-derived cardiomyogenic cells: in vitro expansion and functional improvement in a mouse model of myocardial infarction. Cardiovascular Research, 83(4), 757–767.PubMedCrossRefGoogle Scholar
  29. 29.
    Yu, L. H., Kim, M. H., Park, T. H., et al. (2010). Improvement of cardiac function and remodeling by transplanting adipose tissue-derived stromal cells into a mouse model of acute myocardial infarction. International Journal of Cardiology, 139(2), 166–172.PubMedCrossRefGoogle Scholar
  30. 30.
    Tokunaga, M., Liu, M. L., Nagai, T., et al. (2010). Implantation of cardiac progenitor cells using self-assembling peptide improves cardiac function after myocardial infarction. Journal of Molecular and Cellular Cardiology, 49(6), 972–983.PubMedCrossRefGoogle Scholar
  31. 31.
    Hoke, N. N., Salloum, F. N., Kass, D. A., Das, A., & Kukreja, R. C. (2012). Preconditioning by phosphodiesterase-5 inhibition improves therapeutic efficacy of adipose-derived stem cells following myocardial infarction in mice. Stem Cells, 30(2), 326–335.PubMedCrossRefGoogle Scholar
  32. 32.
    Zhang, Z., Li, S., Cui, M., et al. (2013). Rosuvastatin enhances the therapeutic efficacy of adipose-derived mesenchymal stem cells for myocardial infarction via PI3K/Akt and MEK/ERK pathways. Basic Research in Cardiology, 108(2), 333–0333.PubMedCrossRefGoogle Scholar
  33. 33.
    Li, B., Zeng, Q., Wang, H., et al. (2007). Adipose tissue stromal cells transplantation in rats of acute myocardial infarction. Coronary Artery Disease, 18(3), 221–227.PubMedCrossRefGoogle Scholar
  34. 34.
    Schenke-Layland, K., Strem, B. M., Jordan, M. C., et al. (2009). Adipose tissue-derived cells improve cardiac function following myocardial infarction. Journal of Surgical Research, 153(2), 217–223.PubMedCentralPubMedCrossRefGoogle Scholar
  35. 35.
    Shi, C. Z., Zhang, X. P., Lv, Z. W., et al. (2012). Adipose tissue-derived stem cells embedded with eNOS restore cardiac function in acute myocardial infarction model. International Journal of Cardiology, 154(1), 2–8.PubMedCrossRefGoogle Scholar
  36. 36.
    Paul, A., Nayan, M., Khan, A. A., Shum-Tim, D., & Prakash, S. (2012). Angiopoietin-1-expressing adipose stem cells genetically modified with baculovirus nanocomplex: investigation in rat heart with acute infarction. International Journal of Nanomedicine, 7, 663–682.PubMedCentralPubMedCrossRefGoogle Scholar
  37. 37.
    Liu, Z., Wang, H., Wang, Y., et al. (2012). The influence of chitosan hydrogel on stem cell engraftment, survival and homing in the ischemic myocardial microenvironment. Biomaterials, 33(11), 3093–3106.PubMedCrossRefGoogle Scholar
  38. 38.
    Carvalho, J. L., Braga, V. B., Melo, M. B., et al. (2013). Priming mesenchymal stem cells boosts stem cell therapy to treat myocardial infarction. Journal of Cellular and Molecular Medicine, 17(5), 617–625.PubMedCentralPubMedCrossRefGoogle Scholar
  39. 39.
    Danoviz, M. E., Nakamuta, J. S., Marques, F. L., et al. (2010). Rat adipose tissue-derived stem cells transplantation attenuates cardiac dysfunction post infarction and biopolymers enhance cell retention. PLoS One, 5(8), e12077.PubMedCentralPubMedCrossRefGoogle Scholar
  40. 40.
    Zhu, X. Y., Zhang, X. Z., Xu, L., Zhong, X. Y., Ding, Q., & Chen, Y. X. (2009). Transplantation of adipose-derived stem cells overexpressing hHGF into cardiac tissue. Biochemical and Biophysical Research Communications, 379(4), 1084–1090.PubMedCrossRefGoogle Scholar
  41. 41.
    van Dijk, A., Naaijkens, B. A., Jurgens, W. J. F. M., et al. (2011). Reduction of infarct size by intravenous injection of uncultured adipose derived stromal cells in a rat model is dependent on the time point of application. Stem Cell Research, 7(3), 219–229.PubMedCrossRefGoogle Scholar
  42. 42.
    Wang, L., Deng, J., Tian, W., et al. (2009). Adipose-derived stem cells are an effective cell candidate for treatment of heart failure: an MR imaging study of rat hearts. American Journal of Physiology - Heart and Circulatory Physiology, 297(3), H1020–H1031.PubMedCrossRefGoogle Scholar
  43. 43.
    Hwangbo, S., Kim, J., Her, S., Cho, H., & Lee, J. (2010). Therapeutic potential of human adipose stem cells in a rat myocardial infarction model. Yonsei Medical Journal, 51(1), 69–76.PubMedCentralPubMedCrossRefGoogle Scholar
  44. 44.
    Zhang, X., Wang, H., Ma, X., et al. (2010). Preservation of the cardiac function in infarcted rat hearts by the transplantation of adipose-derived stem cells with injectable fibrin scaffolds. Experimental Biology and Medicine (Maywood, N.J.), 235(12), 1505–1515.CrossRefGoogle Scholar
  45. 45.
    Berardi, G. R., Rebelatto, C. K., Tavares, H. F., et al. (2011). Transplantation of SNAP-treated adipose tissue-derived stem cells improves cardiac function and induces neovascularization after myocardium infarct in rats. Experimental and Molecular Pathology, 90(2), 149–156.PubMedCrossRefGoogle Scholar
  46. 46.
    Karpov, A. A., Uspenskaya, Y. K., Minasian, S. M., et al. (2013). The effect of bone marrow- and adipose tissue-derived mesenchymal stem cell transplantation on myocardial remodelling in the rat model of ischaemic heart failure. International Journal of Experimental Pathology, 94(3), 169–177.PubMedGoogle Scholar
  47. 47.
    Yang, J. J., Yang, X., Liu, Z. Q., et al. (2012). Transplantation of adipose tissue-derived stem cells overexpressing heme oxygenase-1 improves functions and remodeling of infarcted myocardium in rabbits. Tohoku Journal of Experimental Medicine, 226(3), 231–241.PubMedCrossRefGoogle Scholar
  48. 48.
    Alt, E., Pinkernell, K., Scharlau, M., et al. (2010). Effect of freshly isolated autologous tissue resident stromal cells on cardiac function and perfusion following acute myocardial infarction. International Journal of Cardiology, 144(1), 26–35.PubMedCrossRefGoogle Scholar
  49. 49.
    Valina, C., Pinkernell, K., Song, Y. H., et al. (2007). Intracoronary administration of autologous adipose tissue-derived stem cells improves left ventricular function, perfusion, and remodelling after acute myocardial infarction. European Heart Journal, 28(21), 2667–2677.PubMedCrossRefGoogle Scholar
  50. 50.
    De, S. R., Balducci, L., Blasi, A., et al. (2010). Omentum-derived stromal cells improve myocardial regeneration in pig post-infarcted heart through a potent paracrine mechanism. Experimental Cell Research, 316(11), 1804–1815.CrossRefGoogle Scholar
  51. 51.
    Rigol, M., Solanes, N., Farre, J., et al. (2010). Effects of adipose tissue-derived stem cell therapy after myocardial infarction: impact of the route of administration. Journal of Cardiac Failure, 16(4), 357–366.PubMedCrossRefGoogle Scholar
  52. 52.
    Mazo, M., Hernandez, S., Gavira, J. J., et al. (2012). Treatment of reperfused ischemia with adipose-derived stem cells in a preclinical swine model of myocardial infarction. Cell Transplantation, 21(12), 2723–2733.PubMedCrossRefGoogle Scholar
  53. 53.
    Bosma, M. J., & Carroll, A. M. (1991). The SCID mouse mutant: definition, characterization, and potential uses. Annual Review of Immunology, 9, 323–350.PubMedCrossRefGoogle Scholar
  54. 54.
    Cook, J. L., Ikle, D. N., & Routes, B. A. (1995). Natural killer cell ontogeny in the athymic rat. Relationship between functional maturation and acquired resistance to E1A oncogene-expressing sarcoma cells. Journal of Immunology, 155(12), 5512–5518.Google Scholar
  55. 55.
    Bodi, V., Sanchis, J., Nunez, J., et al. (2008). Uncontrolled immune response in acute myocardial infarction: unraveling the thread. American Heart Journal, 156(6), 1065–1073.PubMedCrossRefGoogle Scholar
  56. 56.
    Wang, Q. D., & Sjoquist, P. O. (2006). Myocardial regeneration with stem cells: pharmacological possibilities for efficacy enhancement. Pharmacological Research, 53(4), 331–340.PubMedCrossRefGoogle Scholar
  57. 57.
    Malek, S., Kaplan, E., Wang, J. F., et al. (2006). Successful implantation of intravenously administered stem cells correlates with severity of inflammation in murine myocarditis. Pflügers Archiv, 452(3), 268–275.PubMedCrossRefGoogle Scholar
  58. 58.
    Zaragoza, C., Gomez-Guerrero, C., Martin-Ventura, J. L., et al. (2011). Animal models of cardiovascular diseases. Journal of Biomedicine and Biotechnology, 2011, 497841.PubMedCentralPubMedCrossRefGoogle Scholar
  59. 59.
    Jennings, R., Sommers, H., Smyth, G., Flack, H., & Linn, H. (1960). Myocardial necrosis induced by temporary occlusion of a coronary artery in the dog. Archives of Pathology, 70, 68–78.PubMedGoogle Scholar
  60. 60.
    Yellon, D. M., & Hausenloy, D. J. (2007). Myocardial reperfusion injury. New England Journal of Medicine, 357(11), 1121–1135.PubMedCrossRefGoogle Scholar
  61. 61.
    Krijnen, P. A., Meischl, C., Nijmeijer, R., Visser, C. A., Hack, C. E., & Niessen, H. W. (2006). Inhibition of sPLA2-IIA, C-reactive protein or complement: new therapy for patients with acute myocardial infarction? Cardiovascular & Hematological Disorders Drug Targets, 6(2), 113–123.CrossRefGoogle Scholar
  62. 62.
    Shim, W. S., Tan, G., Gu, Y., et al. (2010). Dose-dependent systolic contribution of differentiated stem cells in post-infarct ventricular function. Journal of Heart and Lung Transplantation, 29(12), 1415–1426.PubMedCrossRefGoogle Scholar
  63. 63.
    Wolf, D., Reinhard, A., Seckinger, A., Katus, H. A., Kuecherer, H., & Hansen, A. (2009). Dose-dependent effects of intravenous allogeneic mesenchymal stem cells in the infarcted porcine heart. Stem Cells and Development, 18(2), 321–329.PubMedCrossRefGoogle Scholar
  64. 64.
    Wei, H., Ooi, T. H., Tan, G., et al. (2010). Cell delivery and tracking in post-myocardial infarction cardiac stem cell therapy: an introduction for clinical researchers. Heart Failure Reviews, 15(1), 1–14.PubMedCrossRefGoogle Scholar
  65. 65.
    Zhu, Y., Liu, T., Song, K., Fan, X., Ma, X., & Cui, Z. (2008). Adipose-derived stem cell: a better stem cell than BMSC. Cell Biochemistry and Function, 26(6), 664–675.PubMedCrossRefGoogle Scholar
  66. 66.
    Fischer, U. M., Harting, M. T., Jimenez, F., et al. (2009). Pulmonary passage is a major obstacle for intravenous stem cell delivery: the pulmonary first-pass effect. Stem Cells and Development, 18(5), 683–692.PubMedCentralPubMedCrossRefGoogle Scholar
  67. 67.
    Houtgraaf, J. H., den Dekker, W. K., van Dalen, B. M., et al. (2012). First experience in humans using adipose tissue-derived regenerative cells in the treatment of patients with ST-segment elevation myocardial infarction. Journal of the American College of Cardiology, 59(5), 539–540.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • B. A. Naaijkens
    • 1
    • 5
    • 6
  • A. van Dijk
    • 1
    • 5
  • O. Kamp
    • 4
    • 5
    • 6
  • P. A. J. Krijnen
    • 1
    • 5
  • H. W. M. Niessen
    • 1
    • 2
    • 5
  • L. J. M. Juffermans
    • 3
    • 4
    • 5
    • 6
  1. 1.Department of PathologyVU University Medical CenterAmsterdamThe Netherlands
  2. 2.Department of Cardiac SurgeryVU University Medical CenterAmsterdamThe Netherlands
  3. 3.Department of PhysiologyVU University Medical CenterAmsterdamThe Netherlands
  4. 4.Department of CardiologyVU University Medical CenterAmsterdamThe Netherlands
  5. 5.Institute of Cardiovascular Research (ICaR-VU)VU University Medical CenterAmsterdamThe Netherlands
  6. 6.Interuniversity Cardiology Institute of the Netherlands (ICIN)UtrechtThe Netherlands

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