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Stem Cells International
Volume 2017, Article ID 9824698, 12 pages
https://doi.org/10.1155/2017/9824698
Research Article

In Vivo Immunogenic Response to Allogeneic Mesenchymal Stem Cells and the Role of Preactivated Mesenchymal Stem Cells Cotransplanted with Allogeneic Islets

1Stem Cell Laboratory, Fundamental Health Science Institute, Universidade Federal Rio Grande do Sul, Porto Alegre, RS, Brazil
2Post Graduate Program in Physiology, Universidade Federal Rio Grande do Sul, Porto Alegre, RS, Brazil
3Fundação Estadual de Produção e Pesquisa em Saúde, Porto Alegre, RS, Brazil
4Hematology and Stem Cell Laboratory, Faculty of Pharmacy, Universidade Federal Rio Grande do Sul, Porto Alegre, RS, Brazil
5Stem Cell Research Institute, Porto Alegre, RS, Brazil

Correspondence should be addressed to Patricia Pranke; rb.sgrfu@eknarpaicirtap

Received 26 October 2016; Revised 6 February 2017; Accepted 8 February 2017; Published 3 May 2017

Academic Editor: Benedetta Bussolati

Copyright © 2017 Régis Linhares Oliveira et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. M. L. Da Silva, P. C. Chagastelles, and N. B. Nardi, “Mesenchymal stem cells reside in virtually all post-natal organs and tissues,” Journal of Cell Science, vol. 119, no. 11, pp. 2204–2213, 2006. View at Publisher · View at Google Scholar · View at Scopus
  2. F. C. Nicola, L. P. Rodrigues, T. Crestani et al., “Human dental pulp stem cells transplantation combined with treadmill training in rats after traumatic spinal cord injury,” Brazilian Journal of Medical and Biological Research, vol. 49, no. 9, pp. 1–11, 2016. View at Publisher · View at Google Scholar · View at Scopus
  3. S. Aggarwal and M. F. Pittenger, “Human mesenchymal stem cells modulate allogeneic immune cell responses,” Transplantation, vol. 105, no. 4, pp. 1815–1822, 2005. View at Publisher · View at Google Scholar
  4. N. M. Di, C. Carlo-stella, M. Magni et al., “Induced by cellular or nonspecific mitogenic stimuli human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli,” vol. 99, no. 10, pp. 3838–3843, 2002. View at Publisher · View at Google Scholar · View at Scopus
  5. J. A. Ankrum, J. F. Ong, and J. M. Karp, “Mesenchymal stem cells: immune evasive, not immune privileged,” Nature Biotechnology, vol. 32, no. 3, pp. 252–260, 2014. View at Publisher · View at Google Scholar · View at Scopus
  6. N. Nagaya, T. Fujii, T. Iwase et al., “Intravenous administration of mesenchymal stem cells improves cardiac function in rats with acute myocardial infarction through angiogenesis and myogenesis,” American Journal of Physiology. Heart and Circulatory Physiology, vol. 287, no. 6, pp. 5–7, 2004. View at Publisher · View at Google Scholar · View at Scopus
  7. M. François, R. Romieu-Mourez, M. Li, and J. Galipeau, “Human MSC suppression correlates with cytokine induction of indoleamine 2,3-dioxygenase and bystander M2 macrophage differentiation,” Molecular Therapy, vol. 20, no. 1, pp. 187–195, 2012. View at Publisher · View at Google Scholar · View at Scopus
  8. M. M. Lalu, L. McIntyre, C. Pugliese et al., “Safety of cell therapy with mesenchymal stromal cells (SafeCell): a systematic review and meta-analysis of clinical trials,” PLoS One, vol. 7, no. 10, article e47559, 2012. View at Publisher · View at Google Scholar · View at Scopus
  9. S. M. Melief, J. J. Zwaginga, W. E. Fibbe, and H. Roelofs, “Adipose tissue-derived multipotent stromal cells have a higher immunomodulatory capacity than their bone marrow-derived counterparts,” Stem Cells Translational Medicine, vol. 2, no. 6, pp. 455–463, 2013. View at Publisher · View at Google Scholar · View at Scopus
  10. W. Ge, J. Jiang, M. L. Baroja et al., “Infusion of mesenchymal stem cells and rapamycin synergize to attenuate alloimmune responses and promote cardiac allograft tolerance,” American Journal of Transplantation, vol. 9, no. 8, pp. 1760–1772, 2009. View at Publisher · View at Google Scholar · View at Scopus
  11. R. Meisel, A. Zibert, M. Laryea, U. Göbel, W. Däubener, and D. Dilloo, “Human bone marrow stromal cells inhibit allogeneic T-cell responses by indoleamine 2,3-dioxygenase-mediated tryptophan degradation,” Blood, vol. 103, no. 12, pp. 4619–4621, 2004. View at Publisher · View at Google Scholar · View at Scopus
  12. G. M. Spaggiari, A. Capobianco, S. Becchetti, M. C. Mingari, and L. Moretta, “Mesenchymal stem cell – natural killer cell interactions: evidence that activated NK cells are capable of killing MSCs, whereas MSCs can inhibit IL-2 – induced NK-cell proliferation,” Blood, vol. 107, no. 4, pp. 1484–1490, 2006. View at Publisher · View at Google Scholar
  13. A. J. Nauta, A. B. Kruisselbrink, E. Lurvink, R. Willemze, and W. E. Fibbe, “Mesenchymal stem cells inhibit generation and function of both CD34+-derived and monocyte-derived dendritic cells,” Journal of Immunology, vol. 177, no. 4, pp. 2080–2087, 2006. View at Publisher · View at Google Scholar
  14. N. Eliopoulos and J. Stagg, “Allogeneic marrow stromal cells are immune rejected by MHC class I–and class II–mismatched recipient mice,” Gene Therapy, vol. 106, no. 13, pp. 4057–4065, 2005. View at Publisher · View at Google Scholar
  15. A. T. Badillo, K. J. Beggs, E. H. Javazon, J. C. Tebbets, and A. W. Flake, “Murine bone marrow stromal progenitor cells elicit an in vivo cellular and humoral alloimmune response,” Biology of Blood and Marrow Transplantation, vol. 13, no. 4, pp. 412–422, 2007. View at Publisher · View at Google Scholar · View at Scopus
  16. A. J. Poncelet, J. Vercruysse, A. Saliez, and P. Gianello, “Although pig allogeneic mesenchymal stem cells are not immunogenic in vitro, intracardiac injection elicits an immune response in vivo,” Transplantation, vol. 83, no. 6, pp. 783–790, 2007. View at Publisher · View at Google Scholar · View at Scopus
  17. M. Seifert, M. Stolk, D. Polenz, and H.-D. Volk, “Detrimental effects of rat mesenchymal stromal cell pre-treatment in a model of acute kidney rejection,” Frontiers in Immunology, vol. 3, no. 202, pp. 1–14, 2012. View at Publisher · View at Google Scholar · View at Scopus
  18. D. M. Camp, D. A. Loeffler, D. M. Farrah, J. N. Borneman, and P. A. LeWitt, “Cellular immune response to intrastriatally implanted allogeneic bone marrow stromal cells in a rat model of Parkinson’s disease,” Journal of Neuroinflammation, vol. 6, no. 1, p. 17, 2009. View at Publisher · View at Google Scholar · View at Scopus
  19. M. D. Griffin, A. E. Ryan, S. Alagesan, P. Lohan, O. Treacy, and T. Ritter, “Anti-donor immune responses elicited by allogeneic mesenchymal stem cells: what have we learned so far?” Immunology and Cell Biology, vol. 91, no. 1, pp. 40–51, 2013. View at Publisher · View at Google Scholar · View at Scopus
  20. K. English, F. P. Barry, C. P. Field-Corbett, and B. P. Mahon, “IFN-γ and TNFα differentially regulate immunomodulation by murine mesenchymal stem cells,” Immunology Letters, vol. 110, no. 2, pp. 91–100, 2007. View at Publisher · View at Google Scholar · View at Scopus
  21. M. J. Crop, C. C. Baan, S. S. Korevaar et al., “Inflammatory conditions affect gene expression and function of human adipose tissue-derived mesenchymal stem cells,” Clinical and Experimental Immunology, vol. 162, no. 3, pp. 474–486, 2010. View at Publisher · View at Google Scholar · View at Scopus
  22. M. Duijvestein, M. E. Wildenberg, M. M. Welling et al., “Pretreatment with interferon-γ enhances the therapeutic activity of mesenchymal stromal cells in animal models of colitis,” Stem Cells, vol. 29, no. 10, pp. 1549–1558, 2011. View at Publisher · View at Google Scholar · View at Scopus
  23. L. M. Tobin, M. E. Healy, K. English, and B. P. Mahon, “Human mesenchymal stem cells suppress donor CD4+ T cell proliferation and reduce pathology in a humanized mouse model of acute graft-versus-host disease,” Clinical and Experimental Immunology, vol. 172, no. 2, pp. 333–348, 2013. View at Publisher · View at Google Scholar · View at Scopus
  24. D. Polchert, J. Sobinsky, G. W. Douglas et al., “IFN-γ activation of mesenchymal stem cells for treatment and prevention of graft versus host disease,” European Journal of Immunology, vol. 38, no. 6, pp. 1745–1755, 2008. View at Publisher · View at Google Scholar · View at Scopus
  25. M. Rafei, E. Birman, K. Forner, and J. Galipeau, “Allogeneic mesenchymal stem cells for treatment of experimental autoimmune encephalomyelitis,” Molecular Therapy, vol. 17, no. 10, pp. 1799–1803, 2009. View at Publisher · View at Google Scholar · View at Scopus
  26. S. Lee, E. Szilagyi, L. Chen et al., “Activated mesenchymal stem cells increase wound tensile strength in aged mouse model via macrophages,” The Journal of Surgical Research, vol. 181, no. 1, pp. 20–24, 2013. View at Publisher · View at Google Scholar · View at Scopus
  27. E. Montaña, S. Bonner-Weir, and G. C. Weir, “Beta cell mass and growth after syngeneic islet cell transplantation in normal and streptozocin diabetic C57BL/6 mice,” The Journal of Clinical Investigation, vol. 91, no. 3, pp. 780–787, 1993. View at Publisher · View at Google Scholar
  28. S. Schu, M. Nosov, L. O’Flynn et al., “Immunogenicity of allogeneic mesenchymal stem cells,” Journal of Cellular and Molecular Medicine, vol. 16, no. 9, pp. 2094–2103, 2012. View at Publisher · View at Google Scholar · View at Scopus
  29. O. Levy, W. Zhao, L. J. Mortensen et al., “mRNA-engineered mesenchymal stem cells for targeted delivery of interleukin-10 to sites of inflammation,” Blood, vol. 122, no. 14, 2013. View at Publisher · View at Google Scholar · View at Scopus
  30. A. S. De la Garza-Rodea, M. C. Verweij, H. Boersma et al., “Exploitation of herpesvirus immune evasion strategies to modify the immunogenicity of human mesenchymal stem cell transplants,” PLoS One, vol. 6, no. 1, article e14493, 2011. View at Publisher · View at Google Scholar · View at Scopus
  31. M. A. Soland, M. G. Bego, E. Colletti et al., “Modulation of human mesenchymal stem cell immunogenicity through forced expression of human cytomegalovirus US proteins,” PLoS One, no. 5, article e36163, p. 7, 2012. View at Publisher · View at Google Scholar
  32. R. S. Waterman, S. L. Tomchuck, S. L. Henkle, and A. M. Betancourt, “A new mesenchymal stem cell (MSC) paradigm: polarization into a pro-inflammatory MSC1 or an immunosuppressive MSC2 phenotype,” PLoS One, vol. 5, no. 4, article e10088, 2010. View at Publisher · View at Google Scholar · View at Scopus
  33. H. Sheng, Y. Wang, Y. Jin et al., “A critical role of IFNgamma in priming MSC-mediated suppression of T cell proliferation through up-regulation of B7-H1,” Cell Research, vol. 18, no. 8, pp. 846–857, 2008. View at Publisher · View at Google Scholar · View at Scopus
  34. M. Krampera, L. Cosmi, R. Angeli et al., “Role for interferon-gamma in the immunomodulatory activity of human bone marrow mesenchymal stem cells,” Stem Cells, vol. 24, no. 2, pp. 386–398, 2006. View at Publisher · View at Google Scholar · View at Scopus
  35. G. Ren, J. Su, L. Zhang et al., “Species variation in the mechanisms of mesenchymal stem cell-mediated immunosuppression,” Stem Cells, vol. 27, no. 8, pp. 1954–1962, 2009. View at Publisher · View at Google Scholar · View at Scopus
  36. H. Wang, F. Qi, X. Dai et al., “Requirement of B7-H1 for immune tolerance to cardiac allografts in combination therapy of mesenchymal stem cells and rapamycin,” Transplant Immunology, vol. 31, no. 2, pp. 1–10, 2014. View at Publisher · View at Google Scholar · View at Scopus
  37. A. Bartholomew, C. Sturgeon, M. Siatskas et al., “Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo,” Experimental Hematology, vol. 30, no. 1, pp. 42–48, 2002. View at Publisher · View at Google Scholar · View at Scopus
  38. R. M. Bingisser, P. A. Tilbrook, P. G. Holt, and U. R. Kees, “Macrophage-derived nitric oxide regulates T cell activation via reversible disruption of the Jak3/STAT5 signaling pathway,” Journal of Immunology, vol. 160, no. 12, pp. 5729–5734, 1998. View at Google Scholar
  39. L. Zangi, R. Margalit, S. Reich-Zeliger et al., “Direct imaging of immune rejection and memory induction by allogeneic mesenchymal stromal cells,” Stem Cells, vol. 27, no. 11, pp. 2865–2874, 2009. View at Publisher · View at Google Scholar · View at Scopus
  40. L. Chen, E. E. Tredget, C. Liu, and Y. Wu, “Analysis of allogenicity of mesenchymal stem cells in engraftment and wound healing in mice,” PLoS One, vol. 4, no. 9, pp. 3–9, 2009. View at Publisher · View at Google Scholar · View at Scopus
  41. J. L. Dembinski, S. M. Wilson, E. L. Spaeth et al., “Tumor stroma engraftment of gene-modified mesenchymal stem cells as anti-tumor therapy against ovarian cancer,” Cytotherapy, vol. 15, no. 1, pp. 20–32, 2013. View at Publisher · View at Google Scholar
  42. G. Moll, I. Rasmusson-Duprez, L. von Bahr et al., “Are therapeutic human mesenchymal stromal cells compatible with human blood?” Stem Cells, vol. 30, no. 7, pp. 1565–1574, 2012. View at Publisher · View at Google Scholar · View at Scopus
  43. J. M. Hare, J. E. Fishman, G. Gerstenblith, and E. Al, “Comparison of allogeneic vs autologous bone marrow–derived mesenchymal stem cells delivered by transendocardial injection in patients with ischemic,” Jama, vol. 308, no. 22, pp. 2369–2379, 2012. View at Publisher · View at Google Scholar · View at Scopus
  44. L. Von Bahr, I. Batsis, G. Moll et al., “Analysis of tissues following mesenchymal stromal cell therapy in humans indicates limited long-term engraftment and no ectopic tissue formation,” Stem Cells, vol. 30, no. 7, pp. 1575–1578, 2012. View at Publisher · View at Google Scholar · View at Scopus
  45. Y. Ding, D. Xu, G. Feng, A. Bushell, R. J. Muschel, and K. J. Wood, “Mesenchymal stem cells prevent the rejection of fully allogenic islet grafts by the immunosuppressive activity of matrix metalloproteinase-2 and -9,” Diabetes, vol. 58, no. 8, pp. 1797–1806, 2009. View at Publisher · View at Google Scholar · View at Scopus
  46. F. R. Li, X. G. Wang, C. Y. Deng, H. Qi, L. L. Ren, and H. X. Zhou, “Immune modulation of co-transplantation mesenchymal stem cells with islet on T and dendritic cells,” Clinical and Experimental Immunology, vol. 161, no. 12, pp. 357–363, 2010. View at Publisher · View at Google Scholar · View at Scopus
  47. J. Guan, Z. Y. Zhang, Z. Q. Zhou, H. Li, D. N. Tong, and G. W. Zhou, “Mesenchymal stem cell modulates T follicular helper cell to induce immunotolerance of islet allograft,” Transplantation Proceedings, vol. 47, no. 6, pp. 2050–2056, 2015. View at Publisher · View at Google Scholar · View at Scopus
  48. Y.-H. Kim and Y.-M. Wee, “Interleukin (IL)-10 induced by CD11b+ cells and IL-10-activated regulatory T cells play a role in immune modulation of mesenchymal stem cells in rat islet allografts,” Molecular Medicine, vol. 17, no. 7-8, pp. 697–708, 2011. View at Publisher · View at Google Scholar · View at Scopus
  49. S. Jacobson, M. Kumagai-Braesch, A. Tibell, M. Svensson, and M. Flodström-Tullberg, “Co-transplantation of stromal cells interferes with the rejection of allogeneic islet grafts,” Annals of the new York Academy of Sciences, vol. 1150, no. 1, pp. 213–216, 2008. View at Publisher · View at Google Scholar · View at Scopus