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Functional Assessment of Adipose Stem Cells for Xenotransplantation Using Myocardial Infarction Immunocompetent Models: Comparison with Bone Marrow Stem Cells

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Abstract

Recently, preclinical studies have shown that allogeneic adipose-derived stem cells (ASCs), like bone marrow-derived mesenchymal stem cell (BMSCs) have significant clinical benefits in treating cardiovascular diseases, such as ischemic/infarcted heart. In this study, we tested whether ASCs are also immune tolerant, such that they can be used as universal donor cells for myocardial regenerative therapy. The study also focuses on investigating the potential therapeutic effects of human ASCs (hASCs) for myocardial infarction in xenotransplant model, and compares its effects with that of hBMSCs. The in vitro study confirms the superior proliferation potential and viability of hASCs under normoxic and stressed hypoxic conditions compared with hBMSCs. hASCs also show higher potential in adopting cardiomyocyte phenotype. The major findings of the in vivo study are that (1) both hASCs and hBMSCs implanted into immunocompetent rat hearts with acute myocardial infarction survived the extreme environment of xenogeneic mismatch for 6 weeks; (2) both hASCs and hBMSCs showed significant improvement in myocardial pro/anti-inflammatory cytokine levels with no detectable inflammatory reaction, despite the lack of any immunosuppressive therapy; and (3) hASCs contributed to the remarkable improvement in cardiac function and reduced infarction which was significantly better than that of hBMSC and untreated control groups. Thus, our findings suggest the feasibility of using ASCs, instead of BMSCs, as universal donor cells for xenogeneic or allogeneic cell therapy.

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References

  1. Lloyd, J. (2010). Heart disease and stroke statistics—2009 update: A report from the American heart association statistics committee and stroke statistics subcommittee (119, e21, 2009). Circulation, 122(1), e11.

  2. Knowlton, K. U., & Chien, K. R. (1999). Inflammatory pathways and cardiac repair: The affliction of infarction. Nature Medicine, 5(10), 1122–1123.

    Article  PubMed  CAS  Google Scholar 

  3. Opie, L. H., Commerford, P. J., Gersh, B. J., & Pfeffer, M. A. (2006). Controversies in cardiology 4—Controversies in ventricular remodelling. Lancet, 367(9507), 356–367.

    Article  PubMed  Google Scholar 

  4. Antonitsis, P., Loannidou-Papagiannaki, E., Kaidogou, A., Charokopos, N., Kalogeridis, A., Kouzi-Koliakou, K., et al. (2008). Cardiomyogenic potential of human adult bone marrow mesenchymal stem cells in vitro. Thoracic and Cardiovascular Surgeon, 56(2), 77–82.

    Article  PubMed  CAS  Google Scholar 

  5. Rota, M., Kajstura, J., Hosoda, T., Bearzi, C., Vitale, S., Esposito, G., et al. (2007). Bone marrow cells adopt the cardiomyogenic fate in vivo. Proceedings of the National Academy of Sciences of the United States of America, 104(45), 17783–17788.

    Article  PubMed  CAS  Google Scholar 

  6. Dengler, T. J., & Katus, H. A. (2002). Stem cell therapy for the infarcted heart (“cellular cardiomyoplasty”). Herz, 27(7), 598–610.

    Article  PubMed  Google Scholar 

  7. Wojakowski, W., & Tendera, M. (2010). New concepts in cardiac stem cell therapy. Hellenic Journal of Cardiology, 51(1), 10–14.

    PubMed  Google Scholar 

  8. Wang, J. S., Shum-Tim, D., Galipeau, J., Chedrawy, E., Eliopoulos, N., & Chiu, R. C. J. (2000). Marrow stromal cells for cellular cardiomyoplasty: Feasibility and potential clinical advantages. Journal of Thoracic and Cardiovascular Surgery, 120(5), 999–1006.

    Article  PubMed  CAS  Google Scholar 

  9. Orlic, D., Kajstura, J., Chimenti, S., Bodine, D. M., Leri, A., Anversa, P., et al. (2001). Transplanted adult bone marrow cells repair myocardial infarcts in mice. Annals of New York Academy of Medicine, 938, 221–230.

    Article  CAS  Google Scholar 

  10. Janssens, S., Dubois, C., Bogaert, J., Theunissen, K., Deroose, C., Desmet, W., et al. (2006). Autologous bone marrow-derived stem-cell transfer in patients with ST-segment elevation myocardial infarction: double-blind, randomised controlled trial. Lancet, 367(9505), 113–121.

    Article  PubMed  Google Scholar 

  11. Zhang, C. Y., Sun, A. J., Zhang, S. N., Yao, K., Wu, C. N., Fu, M. Q., et al. (2010). Efficacy and safety of intracoronary autologous bone marrow-derived cell transplantation in patients with acute myocardial infarction: Insights from randomized controlled trials with 12 or more months follow-up. Clinical Cardiology, 33(6), 353–360.

    Article  PubMed  Google Scholar 

  12. Wollert, K. C., Meyer, G. P., Lotz, J., Ringes-Lichtenberg, S., Lippolt, P., Breidenbach, C., et al. (2004). Intracoronary autologous bone-marrow cell transfer after myocardial infarction: the BOOST randomised controlled clinical trial. Lancet, 364(9429), 141–148.

    Article  PubMed  Google Scholar 

  13. Stamm, C., Liebold, A., Steinhoff, G., & Strunk, D. (2006). Stem cell therapy for ischemic heart disease: Beginning or end of the road? Cell Transplantation, 15, S47–S56.

    Article  PubMed  Google Scholar 

  14. George, J. C. (2010). Stem cell therapy in acute myocardial infarction: A review of clinical trials. Translational Research, 155(1), 10–19.

    Article  PubMed  CAS  Google Scholar 

  15. Atoui, R., Shum-Tim, D., & Chiu, R. C. J. (2008). Myocardial regenerative therapy: Immunologic basis for the potential “universal donor cells”. Annals of Thoracic Surgery, 86(1), 327–334.

    Article  PubMed  Google Scholar 

  16. Atoui, R., Asenjo, J. F., Duong, M., Chen, G., Chiu, R. C. J., & Shum-Tim, D. (2008). Marrow stromal cells as universal donor cells for myocardial regenerative therapy: Their unique immune tolerance. Annals of Thoracic Surgery, 85(2), 571–580.

    Article  PubMed  Google Scholar 

  17. Chen, G. Y., Nayan, M., Duong, M., Asenjo, J. F., Ge, Y., Chiu, R. C. J., et al. (2010). Marrow stromal cells for cell-based therapy: the role of antiinflammatory cytokines in cellular cardiomyoplasty. Annals of Thoracic Surgery, 90(1), 190–198.

    Article  PubMed  Google Scholar 

  18. MacDonald, D. J., Luo, J., Saito, T., Duong, M., Bernier, P. L., Chiu, R. C. J., et al. (2005). Persistence of marrow stromal cells implanted into acutely infarcted myocardium: Observations in a xenotransplant model. Journal of Thoracic and Cardiovascular Surgery, 130(4), 1114–1121.

    Article  PubMed  Google Scholar 

  19. Saito, T., Kuang, J. Q., Bittira, B., Al-Khaldi, A., & Chiu, R. C. J. (2002). Xenotransplant cardiac chimera: Immune tolerance of adult stem cells. Annals of Thoracic Surgery, 74(1), 19–24.

    Article  PubMed  Google Scholar 

  20. Toma, C., Pittenger, M. F., Cahill, K. S., Byrne, B. J., & Kessler, P. D. (2002). Human mesenchymal stem cells differentiate to a cardiomyocyte phenotype in the adult murine heart. Circulation, 105(1), 93–98.

    Article  PubMed  Google Scholar 

  21. Min, J. Y., Sullivan, M. F., Yang, Y., Zhang, J. P., Converso, K. L., Morgan, J. P., et al. (2002). Significant improvement of heart function by cotransplantation of human mesenchymal stem cells and fetal cardiomyocytes in postinfarcted pigs. Annals of Thoracic Surgery, 74(5), 1568–1575.

    Article  PubMed  Google Scholar 

  22. De Ugarte, D. A., Morizono, K., Elbarbary, A., Alfonso, Z., Zuk, P. A., Zhu, M., et al. (2003). Comparison of multi-lineage cells from human adipose tissue and bone marrow. Cells Tissues Organs, 174(3), 101–109.

    Article  PubMed  Google Scholar 

  23. Zuk, P. A., Zhu, M., Ashjian, P., De Ugarte, D. A., Huang, J. I., Mizuno, H., et al. (2002). Human adipose tissue is a source of multipotent stem cells. Molecular Biology of the Cell, 13(12), 4279–4295.

    Article  PubMed  CAS  Google Scholar 

  24. Rehman, J., Traktuev, D., Li, J. L., Merfeld-Clauss, S., Temm-Grove, C. J., Bovenkerk, J. E., et al. (2004). Secretion of angiogenic and antiapoptotic factors by human adipose stromal cells. Circulation, 109(10), 1292–1298.

    Article  PubMed  Google Scholar 

  25. Yu, L. H., Kim, M. H., Park, T. H., Cha, K. S., Kim, Y. D., Quan, M. L., 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.

    Article  PubMed  Google Scholar 

  26. Cai, L. Y., Johnstone, B. H., Cook, T. G., Tan, J., Fishbein, M. C., Chen, P. S., 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.

    Article  PubMed  CAS  Google Scholar 

  27. Paul, A., Shum-Tim, D., & Prakash, S. (2010). Investigation on PEG integrated alginate-chitosan microcapsules for myocardial therapy using marrow stem cells genetically modified by recombinant baculovirus. Cardiovascular Engineering and Technology, 1(2), 154–164.

    Article  Google Scholar 

  28. Rangappa, S., Fen, C., Lee, E. H., Bongso, A., & Wei, E. S. K. (2003). Transformation of adult mesenchymal stem cells isolated from the fatty tissue into cardiomyocytes. Annals of Thoracic Surgery, 75(3), 775–779.

    Article  PubMed  Google Scholar 

  29. Guan, K., Nayernia, K., Maier, L. S., Wagner, S., Dressel, R., Lee, J. H., et al. (2006). Pluripotency of spermatogonial stem cells from adult mouse testis. Nature, 440(7088), 1199–1203.

    Article  PubMed  CAS  Google Scholar 

  30. Paul, A., Ge, Y., Prakash, S., & Shum-Tim, D. (2009). Microencapsulated stem cells for tissue repairing: implications in cell-based myocardial therapy. Regenerative Medicine, 4(5), 733–745.

    Article  PubMed  Google Scholar 

  31. Davani, S., Marandin, A., Mersin, N., Royer, B., Kantelip, B., Herve, P., et al. (2003). Mesenchymal progenitor cells differentiate into an endothelial phenotype, enhance vascular density, and improve heart function in a rat cellular cardiomyoplasty model. Circulation, 108(10), 253–258.

    Google Scholar 

  32. Stumpf, C., Seybold, K., Petzi, S., Wasmeier, G., Raaz, D., Yilmaz, A., et al. (2008). Interleukin-10 improves left ventricular function in rats with heart failure subsequent to myocardial infarction. European Journal of Heart Failure, 10(8), 733–739.

    Article  PubMed  CAS  Google Scholar 

  33. Lee, R. H., Kim, B., Choi, I., Kim, H., Choi, H. S., Suh, K., et al. (2004). Characterization and expression analysis of mesenchymal stem cells from human bone marrow and adipose tissue. Cellular Physiology and Biochemistry, 14(4–6), 311–324.

    Article  PubMed  CAS  Google Scholar 

  34. Choi, Y. S., Dusting, G. J., Stubbs, S., Arunothayaraj, S., Han, X. L., Collas, P., et al. (2010). Differentiation of human adipose-derived stem cells into beating cardiomyocytes. Journal of Cellular and Molecular Medicine, 14(4), 878–889.

    Article  PubMed  CAS  Google Scholar 

  35. Lee, W. C. C., Sepulveda, J. L., Rubin, J. P., & Marra, K. G. (2009). Cardiomyogenic differentiation potential of human adipose precursor cells. International Journal of Cardiology, 133(3), 399–401.

    Article  PubMed  Google Scholar 

  36. Compton, S. J., Cairns, J. A., Holgate, S. T., & Walls, A. F. (1998). The role of mast cell tryptase in regulating endothelial cell proliferation, cytokine release, and adhesion molecule expression: Tryptase induces expression of mRNA for IL-1 beta and IL-8 and stimulates the selective release of IL-8 from human umbilical vein endothelial cells. Journal of Immunology, 161(4), 1939–1946.

    CAS  Google Scholar 

  37. Lacraz, S., Nicod, L. P., Chicheportiche, R., Welgus, H. G., & Dayer, J. M. (1995). Il-10 inhibits metalloproteinase and stimulates Timp-1 production in human mononuclear phagocytes. Journal of Clinical Investigation, 96(5), 2304–2310.

    Article  PubMed  CAS  Google Scholar 

  38. Schenke-Layland, K., Strem, B. M., Jordan, M. C., DeEmedio, M. T., Hedrick, M. H., Roos, K. P., et al. (2009). Adipose tissue-derived cells improve cardiac function following myocardial infarction. Journal of Surgical Research, 153(2), 217–223.

    Article  PubMed  CAS  Google Scholar 

  39. Bai, X. W., Yan, Y. S., Song, Y. H., Droll, L. H., Vykoukal, D., & Alt, E. (2009). Intramyocardial injection of human adipose tissue-derived stem cells improve cardiac function following acute myocardial infarction. Journal of the American College of Cardiology, 53(10), A313.

    Google Scholar 

  40. van der Bogt, K. E. A., Schrepfer, S., Yu, J., Sheikh, A. Y., Hoyt, G., Govaert, J. A., 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.

    Article  PubMed  Google Scholar 

  41. Paul, A., Cantor, A., Shum-Tim, D., & Prakash, S. (2011). Superior cell delivery features of genipin crosslinked polymeric microcapsules: preparation, in vitro characterization and pro-angiogenic applications using human adipose stem cells. Molecular Biotechnology, 48(2), 116–127.

    Article  PubMed  CAS  Google Scholar 

  42. Paul, A., Binsalamah, Z. M., Khan, A. A., Abbasi, S., Elias, C. B., Shum-Tim, D., et al. (2011). A nanobiohybrid complex of recombinant baculovirus and Tat/DNA nanoparticles for delivery of Ang-1 transgene in myocardial infarction therapy. Biomaterials, 32(32), 8304–8318.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The authors would like to thank Minh Duong for her technical assistance in this work. This work is supported in part by research grant from Canadian Institute of Health Research (CIHR; MOP#64308) (to Prakash) and Natural Sciences and Engineering Research Council (NSERC) (To DST, SP and CE) Canada. A.P. acknowledges the financial support from NSERC Alexander Graham Bell Canada Graduate Scholarship.

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Authors and Affiliations

  1. Biomedical Technology and Cell Therapy Research Laboratory, Department of Biomedical Engineering, Faculty of Medicine, McGill University, 3775 University Street, Montreal, QC, H3A 2B4, Canada

    Arghya Paul & Satya Prakash

  2. Divisions of Cardiac Surgery and Surgical Research, The Montreal General Hospital, 1650 Cedar Ave, Montreal, QC, H3G 1A4, Canada

    Sapna Srivastava, Guangyong Chen & Dominique Shum-Tim

  3. Artificial Cells and Organs Research Centre, Faculty of Medicine, McGill University, Montreal, QC, H3G 1Y6, Canada

    Satya Prakash

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  1. Arghya Paul
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Correspondence to Satya Prakash.

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Paul, A., Srivastava, S., Chen, G. et al. Functional Assessment of Adipose Stem Cells for Xenotransplantation Using Myocardial Infarction Immunocompetent Models: Comparison with Bone Marrow Stem Cells. Cell Biochem Biophys 67, 263–273 (2013). https://doi.org/10.1007/s12013-011-9323-0

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