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Stem Cells International
Volume 2015, Article ID 989473, 11 pages
http://dx.doi.org/10.1155/2015/989473
Review Article

Mesenchymal Stromal Cells Affect Disease Outcomes via Macrophage Polarization

1Shaoxing Second Hospital, Shaoxing, Zhejiang 312000, China
2The Children’s Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310052, China
3The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, China

Received 18 May 2015; Accepted 30 June 2015

Academic Editor: Armand Keating

Copyright © 2015 Guoping Zheng 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. A. J. Friedenstein, R. K. Chailakhjan, and K. S. Lalykina, “The development of fibroblast colonies in monolayer cultures of guinea-pig bone marrow and spleen cells,” Cell and Tissue Kinetics, vol. 3, no. 4, pp. 393–403, 1970. View at Google Scholar · View at Scopus
  2. A. I. Caplan, “Mesenchymal stem cells,” Journal of Orthopaedic Research, vol. 9, no. 5, pp. 641–650, 1991. View at Publisher · View at Google Scholar · View at Scopus
  3. M. F. Pittenger, A. M. Mackay, S. C. Beck et al., “Multilineage potential of adult human mesenchymal stem cells,” Science, vol. 284, no. 5411, pp. 143–147, 1999. View at Publisher · View at Google Scholar · View at Scopus
  4. M. D. Griffin, S. J. Elliman, E. Cahill, K. English, R. Ceredig, and T. Ritter, “Concise review: adult mesenchymal stromal cell therapy for inflammatory diseases: how well are we joining the dots?” Stem Cells, vol. 31, no. 10, pp. 2033–2041, 2013. View at Publisher · View at Google Scholar · View at Scopus
  5. G. Maria Spaggiari and L. Moretta, “Cellular and molecular interactions of mesenchymal stem cells in innate immunity,” Immunology and Cell Biology, vol. 91, no. 1, pp. 27–31, 2013. View at Publisher · View at Google Scholar · View at Scopus
  6. K. Le Blanc, F. Frassoni, L. Ball et al., “Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study,” The Lancet, vol. 371, no. 9624, pp. 1579–1586, 2008. View at Publisher · View at Google Scholar · View at Scopus
  7. R. Ciccocioppo, M. E. Bernardo, A. Sgarella et al., “Autologous bone marrow-derived mesenchymal stromal cells in the treatment of fistulising Crohn's disease,” Gut, vol. 60, no. 6, pp. 788–798, 2011. View at Publisher · View at Google Scholar · View at Scopus
  8. J. M. Hare, J. H. Traverse, T. D. Henry et al., “A randomized, double-blind, placebo-controlled, dose-escalation study of intravenous adult human mesenchymal stem cells (prochymal) after acute myocardial infarction,” Journal of the American College of Cardiology, vol. 54, no. 24, pp. 2277–2286, 2009. View at Publisher · View at Google Scholar · View at Scopus
  9. K. Le Blanc, C. Götherström, O. Ringdén et al., “Fetal mesenchymal stem-cell engraftment in bone after in utero transplantation in a patient with severe osteogenesis imperfecta,” Transplantation, vol. 79, no. 11, pp. 1607–1614, 2005. View at Publisher · View at Google Scholar · View at Scopus
  10. G. Zheng, L. Huang, H. Tong et al., “Treatment of acute respiratory distress syndrome with allogeneic adipose-derived mesenchymal stem cells: a randomized, placebo-controlled pilot study,” Respiratory Research, vol. 15, no. 1, article 39, 2014. View at Publisher · View at Google Scholar · View at Scopus
  11. J. A. Thomson, J. Itskovitz-Eldor, S. S. Shapiro et al., “Embryonic stem cell lines derived from human blastocysts,” Science, vol. 282, no. 5391, pp. 1145–1147, 1998. View at Publisher · View at Google Scholar · View at Scopus
  12. S. D. Schwartz, C. D. Regillo, B. L. Lam et al., “Human embryonic stem cell-derived retinal pigment epithelium in patients with age-related macular degeneration and Stargardt's macular dystrophy: Follow-up of two open-label phase 1/2 studies,” The Lancet, vol. 385, no. 9967, pp. 509–516, 2015. View at Publisher · View at Google Scholar · View at Scopus
  13. M. Wernig, J.-P. Zhao, J. Pruszak et al., “Neurons derived from reprogrammed fibroblasts functionally integrate into the fetal brain and improve symptoms of rats with Parkinson's disease,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 15, pp. 5856–5861, 2008. View at Publisher · View at Google Scholar · View at Scopus
  14. J. Hanna, M. Wernig, S. Markoulaki et al., “Treatment of sickle cell anemia mouse model with iPS cells generated from autologous skin,” Science, vol. 318, no. 5858, pp. 1920–1923, 2007. View at Publisher · View at Google Scholar · View at Scopus
  15. K. Okita, T. Ichisaka, and S. Yamanaka, “Generation of germline-competent induced pluripotent stem cells,” Nature, vol. 448, no. 7151, pp. 313–317, 2007. View at Publisher · View at Google Scholar · View at Scopus
  16. P. Cipriani, P. Ruscitti, P. di Benedetto et al., “Mesenchymal stromal cells and rheumatic diseases: new tools from pathogenesis to regenerative therapies,” Cytotherapy, vol. 17, no. 7, pp. 832–849, 2015. View at Publisher · View at Google Scholar · View at Scopus
  17. S. Aggarwal and M. F. Pittenger, “Human mesenchymal stem cells modulate allogeneic immune cell responses,” Blood, vol. 105, no. 4, pp. 1815–1822, 2005. View at Publisher · View at Google Scholar · View at Scopus
  18. M. D. Nicola, C. Carlo-Stella, M. Magni et al., “Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli,” Blood, vol. 99, no. 10, pp. 3838–3843, 2002. View at Publisher · View at Google Scholar · View at Scopus
  19. S. Glennie, I. Soeiro, P. J. Dyson, E. W.-F. Lam, and F. Dazzi, “Bone marrow mesenchymal stem cells induce division arrest anergy of activated T cells,” Blood, vol. 105, no. 7, pp. 2821–2827, 2005. View at Publisher · View at Google Scholar · View at Scopus
  20. S. Ghannam, J. Pene, G. Moquet-Torcy, C. Jorgensen, and H. Yssel, “Mesenchymal stem cells inhibit human Th17 cell differentiation and function and induce a T regulatory cell phenotype,” The Journal of Immunology, vol. 185, pp. 302–312, 2010. View at Google Scholar
  21. S. Asari, S. Itakura, K. Ferreri et al., “Mesenchymal stem cells suppress B-cell terminal differentiation,” Experimental Hematology, vol. 37, no. 5, pp. 604–615, 2009. View at Publisher · View at Google Scholar · View at Scopus
  22. M. Rafei, J. Hsieh, S. Fortier et al., “Mesenchymal stromal cell derived CCL2 suppresses plasma cell immunoglobulin production via STAT3 inactivation and PAX5 induction,” Blood, vol. 112, no. 13, pp. 4991–4998, 2008. View at Publisher · View at Google Scholar · View at Scopus
  23. G. M. Spaggiari, A. Capobianco, H. Abdelrazik, F. Becchetti, M. C. Mingari, and L. Moretta, “Mesenchymal stem cells inhibit natural killer-cell proliferation, cytotoxicity, and cytokine production: role of indoleamine 2,3-dioxygenase and prostaglandin E2,” Blood, vol. 111, no. 3, pp. 1327–1333, 2008. View at Publisher · View at Google Scholar · View at Scopus
  24. S. Beyth, Z. Borovsky, D. Mevorach et al., “Human mesenchymal stem cells alter antigen-presenting cell maturation and induce T-cell unresponsiveness,” Blood, vol. 105, no. 5, pp. 2214–2219, 2005. View at Publisher · View at Google Scholar · View at Scopus
  25. J. Kim and P. Hematti, “Mesenchymal stem cell-educated macrophages: a novel type of alternatively activated macrophages,” Experimental Hematology, vol. 37, no. 12, pp. 1445–1453, 2009. View at Publisher · View at Google Scholar · View at Scopus
  26. M. Gazdic, V. Volarevic, N. Arsenijevic, and M. Stojkovic, “Mesenchymal stem cells: a friend or foe in immune-mediated diseases,” Stem Cell Reviews and Reports, vol. 11, no. 2, pp. 280–287, 2015. View at Publisher · View at Google Scholar · View at Scopus
  27. M. Dominici, K. Le Blanc, I. Mueller et al., “Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement,” Cytotherapy, vol. 8, no. 4, pp. 315–317, 2006. View at Publisher · View at Google Scholar · View at Scopus
  28. G. C. Kopen, D. J. Prockop, and D. G. Phinney, “Marrow stromal cells migrate throughout forebrain and cerebellum, and they differentiate into astrocytes after injection into neonatal mouse brains,” Proceedings of the National Academy of Sciences of the United States of America, vol. 96, no. 19, pp. 10711–10716, 1999. View at Publisher · View at Google Scholar · View at Scopus
  29. F. Ezquer, M. Ezquer, D. Contador, M. Ricca, V. Simon, and P. Conget, “The antidiabetic effect of mesenchymal stem cells is unrelated to their transdifferentiation potential but to their capability to restore Th1/Th2 balance and to modify the pancreatic microenvironment,” Stem Cells, vol. 30, no. 8, pp. 1664–1674, 2012. View at Publisher · View at Google Scholar · View at Scopus
  30. F. Mosna, L. Sensebé, and M. Krampera, “Human bone marrow and adipose tissue mesenchymal stem cells: a user's guide,” Stem Cells and Development, vol. 19, no. 10, pp. 1449–1470, 2010. View at Publisher · View at Google Scholar · View at Scopus
  31. O. K. Lee, T. K. Kuo, W.-M. Chen, K.-D. Lee, S.-L. Hsieh, and T.-H. Chen, “Isolation of multipotent mesenchymal stem cells from umbilical cord blood,” Blood, vol. 103, no. 5, pp. 1669–1675, 2004. View at Publisher · View at Google Scholar · View at Scopus
  32. S. Kern, H. Eichler, J. Stoeve, H. Klüter, and K. Bieback, “Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue,” Stem Cells, vol. 24, no. 5, pp. 1294–1301, 2006. View at Publisher · View at Google Scholar · View at Scopus
  33. 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 ID e10088, 2010. View at Publisher · View at Google Scholar · View at Scopus
  34. K. Le Blanc, C. Tammik, K. Rosendahl, E. Zetterberg, and O. Ringdén, “HLA expression and immunologic properties of differentiated and undifferentiated mesenchymal stem cells,” Experimental Hematology, vol. 31, no. 10, pp. 890–896, 2003. View at Publisher · View at Google Scholar · View at Scopus
  35. K. Le Blanc, L. Tammik, B. Sundberg, S. E. Haynesworth, and O. Ringdén, “Mesenchymal stem cells inhibit and stimulate mixed lymphocyte cultures and mitogenic responses independently of the major histocompatibility complex,” Scandinavian Journal of Immunology, vol. 57, no. 1, pp. 11–20, 2003. View at Publisher · View at Google Scholar · View at Scopus
  36. K. McIntosh, S. Zvonic, S. Garrett et al., “The immunogenicity of human adipose-derived cells: temporal changes in vitro,” Stem Cells, vol. 24, no. 5, pp. 1246–1253, 2006. View at Publisher · View at Google Scholar · View at Scopus
  37. C. Toma, M. F. Pittenger, K. S. Cahill, B. J. Byrne, and P. D. Kessler, “Human mesenchymal stem cells differentiate to a cardiomyocyte phenotype in the adult murine heart,” Circulation, vol. 105, no. 1, pp. 93–98, 2002. View at Publisher · View at Google Scholar · View at Scopus
  38. H. C. Quevedo, K. E. Hatzistergos, B. N. Oskouei et al., “Allogeneic mesenchymal stem cells restore cardiac function in chronic ischemic cardiomyopathy via trilineage differentiating capacity,” Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 33, pp. 14022–14027, 2009. View at Publisher · View at Google Scholar · View at Scopus
  39. A. Monsel, Y.-G. Zhu, S. Gennai, Q. Hao, J. Liu, and J. W. Lee, “Cell-based therapy for acute organ injury: preclinical evidence and ongoing clinical trials using mesenchymal stem cells,” Anesthesiology, vol. 121, no. 5, pp. 1099–1121, 2014. View at Publisher · View at Google Scholar · View at Scopus
  40. R. H. Lee, A. A. Pulin, M. J. Seo et al., “Intravenous hMSCs improve myocardial infarction in mice because cells embolized in lung are activated to secrete the anti-inflammatory protein TSG-6,” Cell Stem Cell, vol. 5, no. 1, pp. 54–63, 2009. View at Publisher · View at Google Scholar · View at Scopus
  41. M. B. Herrera, B. Bussolati, S. Bruno et al., “Exogenous mesenchymal stem cells localize to the kidney by means of CD44 following acute tubular injury,” Kidney International, vol. 72, no. 4, pp. 430–441, 2007. View at Publisher · View at Google Scholar · View at Scopus
  42. F. Tögel, J. Isaac, Z. Hu, K. Weiss, and C. Westenfelder, “Renal SDF-1 signals mobilization and homing of CXCR4-positive cells to the kidney after ischemic injury,” Kidney International, vol. 67, no. 5, pp. 1772–1784, 2005. View at Publisher · View at Google Scholar · View at Scopus
  43. C. Xinaris, M. Morigi, V. Benedetti et al., “A novel strategy to enhance mesenchymal stem cell migration capacity and promote tissue repair in an injury specific fashion,” Cell Transplantation, vol. 22, no. 3, pp. 423–436, 2013. View at Publisher · View at Google Scholar · View at Scopus
  44. S.-C. Hung, R. R. Pochampally, S.-C. Hsu et al., “Short-term exposure of multipotent stromal cells to low oxygen increases their expression of CX3CR1 and CXCR4 and their engraftment in vivo,” PLoS ONE, vol. 2, no. 5, article e416, 2007. View at Publisher · View at Google Scholar · View at Scopus
  45. Z. Cheng, L. Ou, X. Zhou et al., “Targeted migration of mesenchymal stem cells modified with CXCR4 gene to infarcted myocardium improves cardiac performance,” Molecular Therapy, vol. 16, no. 3, pp. 571–579, 2008. View at Publisher · View at Google Scholar · View at Scopus
  46. F. Tögel, Z. Hu, K. Weiss, J. Isaac, C. Lange, and C. Westenfelder, “Administered mesenchymal stem cells protect against ischemic acute renal failure through differentiation-independent mechanisms,” The American Journal of Physiology—Renal Physiology, vol. 289, no. 1, pp. F31–F42, 2005. View at Publisher · View at Google Scholar · View at Scopus
  47. P. Burra, D. Arcidiacono, D. Bizzaro et al., “Systemic administration of a novel human umbilical cord mesenchymal stem cells population accelerates the resolution of acute liver injury,” BMC Gastroenterology, vol. 12, article 88, 2012. View at Publisher · View at Google Scholar · View at Scopus
  48. J. Xu, C. R. Woods, A. L. Mora et al., “Prevention of endotoxin-induced systemic response by bone marrow-derived mesenchymal stem cells in mice,” American Journal of Physiology—Lung Cellular and Molecular Physiology, vol. 293, no. 1, pp. L131–L141, 2007. View at Publisher · View at Google Scholar · View at Scopus
  49. S. Y. Ahn, Y. S. Chang, D. K. Sung et al., “Mesenchymal stem cells prevent hydrocephalus after severe intraventricular hemorrhage,” Stroke, vol. 44, no. 2, pp. 497–504, 2013. View at Publisher · View at Google Scholar · View at Scopus
  50. S. H. J. Mei, J. J. Haitsma, C. C. Dos Santos et al., “Mesenchymal stem cells reduce inflammation while enhancing bacterial clearance and improving survival in sepsis,” American Journal of Respiratory and Critical Care Medicine, vol. 182, no. 8, pp. 1047–1057, 2010. View at Publisher · View at Google Scholar · View at Scopus
  51. K. Le Blanc and D. Mougiakakos, “Multipotent mesenchymal stromal cells and the innate immune system,” Nature Reviews Immunology, vol. 12, no. 5, pp. 383–396, 2012. View at Publisher · View at Google Scholar · View at Scopus
  52. W. Ge, J. Jiang, J. Arp, W. Liu, B. Garcia, and H. Wang, “Regulatory T-cell generation and kidney allograft tolerance induced by mesenchymal stem cells associated with indoleamine 2,3-dioxygenase expression,” Transplantation, vol. 90, no. 12, pp. 1312–1320, 2010. View at Publisher · View at Google Scholar · View at Scopus
  53. K. Németh, A. Leelahavanichkul, P. S. T. Yuen et al., “Bone marrow stromal cells attenuate sepsis via prostaglandin E2-dependent reprogramming of host macrophages to increase their interleukin-10 production,” Nature Medicine, vol. 15, no. 1, pp. 42–49, 2009. View at Publisher · View at Google Scholar · View at Scopus
  54. K. Nemeth, A. Keane-Myers, J. M. Brown et al., “Bone marrow stromal cells use TGF-β to suppress allergic responses in a mouse model of ragweed-induced asthma,” Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 12, pp. 5652–5657, 2010. View at Publisher · View at Google Scholar · View at Scopus
  55. L. A. Ortiz, M. DuTreil, C. Fattman et al., “Interleukin 1 receptor antagonist mediates the antiinflammatory and antifibrotic effect of mesenchymal stem cells during lung injury,” Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 26, pp. 11002–11007, 2007. View at Publisher · View at Google Scholar · View at Scopus
  56. S. Danchuk, J. H. Ylostalo, F. Hossain et al., “Human multipotent stromal cells attenuate lipopolysaccharide-induced acute lung injury in mice via secretion of tumor necrosis factor-α-induced protein 6,” Stem Cell Research and Therapy, vol. 2, no. 3, article 27, 2011. View at Publisher · View at Google Scholar · View at Scopus
  57. K. Sato, K. Ozaki, I. Oh et al., “Nitric oxide plays a critical role in suppression of T-cell proliferation by mesenchymal stem cells,” Blood, vol. 109, no. 1, pp. 228–234, 2007. View at Publisher · View at Google Scholar · View at Scopus
  58. K. Akiyama, C. Chen, D. Wang et al., “Mesenchymal-stem-cell-induced immunoregulation involves FAS-ligand-/FAS-mediated T cell apoptosis,” Cell Stem Cell, vol. 10, no. 5, pp. 544–555, 2012. View at Publisher · View at Google Scholar
  59. Y.-P. Li, S. Paczesny, E. Lauret et al., “Human mesenchymal stem cells license adult CD34+ hemopoietic progenitor cells to differentiate into regulatory dendritic cells through activation of the notch pathway,” Journal of Immunology, vol. 180, no. 3, pp. 1598–1608, 2008. View at Publisher · View at Google Scholar · View at Scopus
  60. M. Krampera, S. Glennie, J. Dyson et al., “Bone marrow mesenchymal stem cells inhibit the response of naive and memory antigen-specific T cells to their cognate peptide,” Blood, vol. 101, no. 9, pp. 3722–3729, 2003. View at Publisher · View at Google Scholar · View at Scopus
  61. 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
  62. M. Krampera, L. Cosmi, R. Angeli et al., “Role for interferon-γ 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
  63. M. M. Duffy, J. Pindjakova, S. A. Hanley et al., “Mesenchymal stem cell inhibition of T-helper 17 cell- differentiation is triggered by cell-cell contact and mediated by prostaglandin E2 via the EP4 receptor,” European Journal of Immunology, vol. 41, no. 10, pp. 2840–2851, 2011. View at Publisher · View at Google Scholar · View at Scopus
  64. B. del Papa, P. Sportoletti, D. Cecchini et al., “Notch1 modulates mesenchymal stem cells mediated regulatory T-cell induction,” European Journal of Immunology, vol. 43, no. 1, pp. 182–187, 2013. View at Publisher · View at Google Scholar · View at Scopus
  65. Z. Selmani, A. Naji, I. Zidi et al., “Human leukocyte antigen-G5 secretion by human mesenchymal stem cells is required to suppress T lymphocyte and natural killer function and to induce CD4+CD25highFOXP3+ regulatory T cells,” Stem Cells, vol. 26, no. 1, pp. 212–222, 2008. View at Google Scholar
  66. K. English, J. M. Ryan, L. Tobin, M. J. Murphy, F. P. Barry, and B. P. Mahon, “Cell contact, prostaglandin E2 and transforming growth factor beta 1 play non-redundant roles in human mesenchymal stem cell induction of CD4+CD25Highforkhead box P3+ regulatory T cells,” Clinical & Experimental Immunology, vol. 156, no. 1, pp. 149–160, 2009. View at Publisher · View at Google Scholar · View at Scopus
  67. H. Kavanagh and B. P. Mahon, “Allogeneic mesenchymal stem cells prevent allergic airway inflammation by inducing murine regulatory T cells,” Allergy, vol. 66, no. 4, pp. 523–531, 2011. View at Publisher · View at Google Scholar · View at Scopus
  68. M. Li, X. Sun, X. Kuang, Y. Liao, H. Li, and D. Luo, “Mesenchymal stem cells suppress CD8+ T cell-mediated activation by suppressing natural killer group 2, member D protein receptor expression and secretion of prostaglandin E2, indoleamine 2, 3-dioxygenase and transforming growth factor-beta,” Clinical and Experimental Immunology, vol. 178, no. 3, pp. 516–524, 2014. View at Publisher · View at Google Scholar · View at Scopus
  69. 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,” The Journal of Immunology, vol. 177, no. 4, pp. 2080–2087, 2006. View at Publisher · View at Google Scholar · View at Scopus
  70. R. Ramasamy, H. Fazekasova, E. W.-F. Lam, I. Soeiro, G. Lombardi, and F. Dazzi, “Mesenchymal stem cells inhibit dendritic cell differentiation and function by preventing entry into the cell cycle,” Transplantation, vol. 83, no. 1, pp. 71–76, 2007. View at Publisher · View at Google Scholar · View at Scopus
  71. X.-X. Jiang, Y. Zhang, B. Liu et al., “Human mesenchymal stem cells inhibit differentiation and function of monocyte-derived dendritic cells,” Blood, vol. 105, no. 10, pp. 4120–4126, 2005. View at Publisher · View at Google Scholar · View at Scopus
  72. P. A. Sotiropoulou, S. A. Perez, A. D. Gritzapis, C. N. Baxevanis, and M. Papamichail, “Interactions between human mesenchymal stem cells and natural killer cells,” Stem Cells, vol. 24, no. 1, pp. 74–85, 2006. View at Publisher · View at Google Scholar · View at Scopus
  73. I. Rasmusson, O. Ringdén, B. Sundberg, and K. Le Blanc, “Mesenchymal stem cells inhibit the formation of cytotoxic T lymphocytes, but not activated cytotoxic T lymphocytes or natural killer cells,” Transplantation, vol. 76, no. 8, pp. 1208–1213, 2003. View at Publisher · View at Google Scholar · View at Scopus
  74. 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 · View at Scopus
  75. M. Giuliani, A. Bennaceur-Griscelli, A. Nanbakhsh et al., “TLR ligands stimulation protects MSC from NK killing,” Stem Cells, vol. 32, no. 1, pp. 290–300, 2014. View at Publisher · View at Google Scholar · View at Scopus
  76. E. Muraille, O. Leo, and M. Moser, “Th1/Th2 paradigm extended: macrophage polarization as an unappreciated pathogen-driven escape mechanism?” Frontiers in Immunology, vol. 5, article 603, 2014. View at Publisher · View at Google Scholar · View at Scopus
  77. A. Mantovani, S. K. Biswas, M. R. Galdiero, A. Sica, and M. Locati, “Macrophage plasticity and polarization in tissue repair and remodelling,” The Journal of Pathology, vol. 229, no. 2, pp. 176–185, 2013. View at Publisher · View at Google Scholar · View at Scopus
  78. M. Stein, S. Keshav, N. Harris, and S. Gordon, “Interleukin 4 potently enhances murine macrophage mannose receptor activity: a marker of alternative immunologic macrophage activation,” Journal of Experimental Medicine, vol. 176, no. 1, pp. 287–292, 1992. View at Publisher · View at Google Scholar · View at Scopus
  79. S. K. Biswas and A. Mantovani, “Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm,” Nature Immunology, vol. 11, no. 10, pp. 889–896, 2010. View at Publisher · View at Google Scholar · View at Scopus
  80. M. Peled and E. A. Fisher, “Dynamic aspects of macrophage polarization during atherosclerosis progression and regression,” Frontiers in Immunology, vol. 5, article 579, 2014. View at Publisher · View at Google Scholar · View at Scopus
  81. R. Parsa, P. Andresen, A. Gillett et al., “Adoptive transfer of immunomodulatory M2 macrophages prevents type 1 diabetes in NOD mice,” Diabetes, vol. 61, no. 11, pp. 2881–2892, 2012. View at Publisher · View at Google Scholar · View at Scopus
  82. P. J. Murray, J. E. Allen, S. K. Biswas et al., “Macrophage activation and polarization: nomenclature and experimental guidelines,” Immunity, vol. 41, no. 1, pp. 14–20, 2014. View at Publisher · View at Google Scholar · View at Scopus
  83. M. M. Tiemessen, A. L. Jagger, H. G. Evans, M. J. C. van Herwijnen, S. John, and L. S. Taams, “CD4+CD25+Foxp3+ regulatory T cells induce alternative activation of human monocytes/macrophages,” Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 49, pp. 19446–19451, 2007. View at Publisher · View at Google Scholar · View at Scopus
  84. G. Raes, A. Beschin, G. H. Ghassabeh, and P. De Baetselier, “Alternatively activated macrophages in protozoan infections,” Current Opinion in Immunology, vol. 19, no. 4, pp. 454–459, 2007. View at Publisher · View at Google Scholar · View at Scopus
  85. F. O. Martinez, A. Sica, A. Mantovani, and M. Locati, “Macrophage activation and polarization,” Frontiers in Bioscience, vol. 13, no. 2, pp. 453–461, 2008. View at Publisher · View at Google Scholar · View at Scopus
  86. M. E. Shaul, G. Bennett, K. J. Strissel, A. S. Greenberg, and M. S. Obin, “Dynamic, M2-like remodeling phenotypes of CD11c+ adipose tissue macrophages during high-fat diet—induced obesity in mice,” Diabetes, vol. 59, no. 5, pp. 1171–1181, 2010. View at Publisher · View at Google Scholar · View at Scopus
  87. H. Choi, R. H. Lee, N. Bazhanov, J. Y. Oh, and D. J. Prockop, “Anti-inflammatory protein TSG-6 secreted by activated MSCs attenuates zymosan-induced mouse peritonitis by decreasing TLR2/NF-kappaB signaling in resident macrophages,” Blood, vol. 118, no. 2, pp. 330–338, 2011. View at Publisher · View at Google Scholar · View at Scopus
  88. S. M. Melief, S. B. Geutskens, W. E. Fibbe, and H. Roelofs, “Multipotent stromal cells skew monocytes towards an anti-inflammatory interleukin-10-producing phenotype by production of interleukin-6,” Haematologica, vol. 98, no. 6, pp. 888–895, 2013. View at Publisher · View at Google Scholar · View at Scopus
  89. 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
  90. S. M. Melief, E. Schrama, M. H. Brugman et al., “Multipotent stromal cells induce human regulatory T cells through a novel pathway involving skewing of monocytes toward anti-inflammatory macrophages,” Stem Cells, vol. 31, no. 9, pp. 1980–1991, 2013. View at Publisher · View at Google Scholar · View at Scopus
  91. Q.-Z. Zhang, W.-R. Su, S.-H. Shi et al., “Human gingiva-derived mesenchymal stem cells elicit polarization of M2 macrophages and enhance cutaneous wound healing,” Stem Cells, vol. 28, no. 10, pp. 1856–1868, 2010. View at Publisher · View at Google Scholar · View at Scopus
  92. R. Shohara, A. Yamamoto, S. Takikawa et al., “Mesenchymal stromal cells of human umbilical cord Wharton's jelly accelerate wound healing by paracrine mechanisms,” Cytotherapy, vol. 14, no. 10, pp. 1171–1181, 2012. View at Publisher · View at Google Scholar · View at Scopus
  93. D. Jiang, Y. Qi, N. G. Walker et al., “The effect of adipose tissue derived MSCs delivered by a chemically defined carrier on full-thickness cutaneous wound healing,” Biomaterials, vol. 34, no. 10, pp. 2501–2515, 2013. View at Publisher · View at Google Scholar · View at Scopus
  94. S. H. Mei, S. D. McCarter, Y. Deng, C. H. Parker, W. C. Liles, and D. J. Stewart, “Prevention of LPS-induced acute lung injury in mice by mesenchymal stem cells overexpressing angiopoietin 1,” PLoS Medicine, vol. 4, no. 9, article e269, 2007. View at Google Scholar
  95. L. Ionescu, R. N. Byrne, T. van Haaften et al., “Stem cell conditioned medium improves acute lung injury in mice: in vivo evidence for stem cell paracrine action,” The American Journal of Physiology—Lung Cellular and Molecular Physiology, vol. 303, no. 11, pp. L967–L977, 2012. View at Publisher · View at Google Scholar · View at Scopus
  96. T. Maron-Gutierrez, J. D. Silva, K. D. Asensi et al., “Effects of mesenchymal stem cell therapy on the time course of pulmonary remodeling depend on the etiology of lung injury in mice,” Critical Care Medicine, vol. 41, no. 11, pp. e319–e333, 2013. View at Publisher · View at Google Scholar · View at Scopus
  97. M. A. Antunes, S. C. Abreu, F. F. Cruz et al., “Effects of different mesenchymal stromal cell sources and delivery routes in experimental emphysema,” Respiratory Research, vol. 15, no. 1, article 118, 2014. View at Publisher · View at Google Scholar · View at Scopus
  98. V. Dayan, G. Yannarelli, F. Billia et al., “Mesenchymal stromal cells mediate a switch to alternatively activated monocytes/macrophages after acute myocardial infarction,” Basic Research in Cardiology, vol. 106, no. 6, pp. 1299–1310, 2011. View at Publisher · View at Google Scholar · View at Scopus
  99. S. Ishikane, H. Hosoda, K. Yamahara et al., “Allogeneic transplantation of fetal membrane-derived mesenchymal stem cell sheets increases neovascularization and improves cardiac function after myocardial infarction in rats,” Transplantation, vol. 96, no. 8, pp. 697–706, 2013. View at Publisher · View at Google Scholar · View at Scopus
  100. T. Ben-Mordechai, R. Holbova, N. Landa-Rouben et al., “Macrophage subpopulations are essential for infarct repair with and without stem cell therapy,” Journal of the American College of Cardiology, vol. 62, no. 20, pp. 1890–1901, 2013. View at Publisher · View at Google Scholar · View at Scopus
  101. S. Adutler-Lieber, T. Ben-Mordechai, N. Naftali-Shani et al., “Human macrophage regulation via interaction with cardiac adipose tissue-derived mesenchymal stromal cells,” Journal of Cardiovascular Pharmacology and Therapeutics, vol. 18, no. 1, pp. 78–86, 2013. View at Publisher · View at Google Scholar · View at Scopus
  102. W. Li, Q. Zhang, M. Wang et al., “Macrophages are involved in the protective role of human umbilical cord-derived stromal cells in renal ischemia-reperfusion injury,” Stem Cell Research, vol. 10, no. 3, pp. 405–416, 2013. View at Publisher · View at Google Scholar · View at Scopus
  103. M. M. Duffy, B. A. McNicholas, D. A. Monaghan et al., “Mesenchymal stem cells and a vitamin D receptor agonist additively suppress T helper 17 cells and the related inflammatory response in the kidney,” The American Journal of Physiology—Renal Physiology, vol. 307, no. 12, pp. F1412–F1426, 2014. View at Publisher · View at Google Scholar · View at Scopus
  104. A. F. Wise, T. M. Williams, M. B. G. Kiewiet et al., “Human mesenchymal stem cells alter macrophage phenotype and promote regeneration via homing to the kidney following ischemia-reperfusion injury,” The American Journal of Physiology—Renal Physiology, vol. 306, no. 10, pp. F1222–F1235, 2014. View at Publisher · View at Google Scholar · View at Scopus
  105. Y. Geng, L. Zhang, B. Fu et al., “Mesenchymal stem cells ameliorate rhabdomyolysis-induced acute kidney injury via the activation of M2 macrophages,” Stem Cell Research and Therapy, vol. 5, no. 3, article 80, 2014. View at Publisher · View at Google Scholar · View at Scopus
  106. H. Nakajima, K. Uchida, A. R. Guerrero et al., “Transplantation of mesenchymal stem cells promotes an alternative pathway of macrophage activation and functional recovery after spinal cord injury,” Journal of Neurotrauma, vol. 29, no. 8, pp. 1614–1625, 2012. View at Publisher · View at Google Scholar · View at Scopus
  107. J. Barminko, J. H. Kim, S. Otsuka et al., “Encapsulated mesenchymal stromal cells for in vivo transplantation,” Biotechnology and Bioengineering, vol. 108, no. 11, pp. 2747–2758, 2011. View at Publisher · View at Google Scholar · View at Scopus
  108. K. Matsubara, Y. Matsushita, K. Sakai et al., “Secreted ectodomain of sialic acid-binding Ig-like lectin-9 and monocyte chemoattractant protein-1 promote recovery after rat spinal cord injury by altering macrophage polarity,” Journal of Neuroscience, vol. 35, no. 6, pp. 2452–2464, 2015. View at Publisher · View at Google Scholar · View at Scopus
  109. E. R. Zanier, F. Pischiutta, L. Riganti et al., “Bone marrow mesenchymal stromal cells drive protective M2 microglia polarization after brain trauma,” Neurotherapeutics, vol. 11, no. 3, pp. 679–695, 2014. View at Publisher · View at Google Scholar · View at Scopus