본문 바로가기
KERD
논문KCI 등재

Preclinical Efficacy and Mechanisms of Mesenchymal Stem Cells in Animal Models of Autoimmune Diseases

1

조회

0

다운로드

0

인용

0

참고문헌

키워드

초록

Mesenchymal stem cells (MSCs) are present in diverse tissues and organs, including bone marrow, umbilical cord, adipose tissue, and placenta. MSCs can expand easily in vitro and have regenerative stem cell properties and potent immunoregulatory activity. They inhibit the functions of dendritic cells, B cells, and T cells, but enhance those of regulatory T cells by producing immunoregulatory molecules such as transforming growth factor-β, hepatic growth factors, prostaglandin E2, interleukin-10, indolamine 2,3-dioxygenase, nitric oxide, heme oxygenase-1, and human leukocyte antigen-G. These properties make MSCs promising therapeutic candidates for the treatment of autoimmune diseases. Here, we review the preclinical studies of MSCs in animal models for systemic lupus erythematosus, rheumatoid arthritis, Crohn’s disease, and experimental autoimmune encephalomyelitis, and summarize the underlying immunoregulatory mechanisms.

Abstract

Mesenchymal stem cells (MSCs) are present in diverse tissues and organs, including bone marrow, umbilical cord, adipose tissue, and placenta. MSCs can expand easily in vitro and have regenerative stem cell properties and potent immunoregulatory activity. They inhibit the functions of dendritic cells, B cells, and T cells, but enhance those of regulatory T cells by producing immunoregulatory molecules such as transforming growth factor-β, hepatic growth factors, prostaglandin E2, interleukin-10, indolamine 2,3-dioxygenase, nitric oxide, heme oxygenase-1, and human leukocyte antigen-G. These properties make MSCs promising therapeutic candidates for the treatment of autoimmune diseases. Here, we review the preclinical studies of MSCs in animal models for systemic lupus erythematosus, rheumatoid arthritis, Crohn’s disease, and experimental autoimmune encephalomyelitis, and summarize the underlying immunoregulatory mechanisms.

참고문헌 (51)

  1. Watt, F. M., "Out of Eden : stem cells and their niches", Science, 287, pp.1427~1430 (2000)
  2. Thomson, J. A., "Embryonic stem cell lines derived from human blastocysts", Science, 282, pp.1145~1147 (1998)
  3. Friedenstein, A. J., "The development of fibroblast colonies in monolayer cultures of guinea-pig bone marrow and spleen cells", Cell Tissue Kinet, 3, pp.393~403 (1970)
  4. Nussbaum, J., "Transplantation of undifferentiated murine embryonic stem cells in the heart: teratoma formation and immune response", FASEB. J, 21, pp.1345~1357 (2007)
  5. Kon, E, "Autologous bone marrow stromal cells loaded onto porous hydroxyapatite ceramic accelerate bone repair in critical-size defects of sheep long bones", J. Biomed. Mater. Res, 49, pp.328~337 (2000)
  6. Solchaga, L. A., "Repair of osteochondral defects with hyaluronan-and polyester-based scaffolds", Osteoarthritis Cartilage, 13, pp.297~309 (2005)
  7. Horwitz, E. M, "Clarification of the nomenclature for MSC: The International Society for Cellular Therapy position statement", Cytotherapy, 7, pp.393~395 (2005)
  8. Dominici, M., "Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement", Cytotherapy, 8, pp.315~317 (2006)
  9. Amado, L. C, "Cardiac repair with intramyocardial injection of allogeneic mesenchymal stem cells after myocardial infarction", Proc. Natl. Acad. Sci. USA, 102, pp.11474~11479 (2005)
  10. Lin, Y. T, "Human mesenchymal stem cells prolong survival and ameliorate motor deficit through trophic support in Huntington's disease mouse models", PLoS One, 6, pp.e22924~ (2011)
  11. Miyahara, Y, "Monolayered mesenchymal stem cells repair scarred myocardium after myocardial infarction", Nat. Med, 12, pp.459~465 (2006)
  12. Ball, L. M., "Cotransplantation of ex vivo expanded mesenchymal stem cells accelerates lymphocyte recovery and may reduce the risk of graft failure in haploidentical hematopoietic stem-cell transplantation", Blood, 110, pp.2764~2767 (2007)
  13. Le Blanc, K, "Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease : a phase II study", Lancet, 371, pp.1579~1586 (2008)
  14. Duijvestein, M, "Autologous bone marrow-derived mesenchymal stromal cell treatment for refractory luminal Crohn's disease : results of a phase I study", Gut, 59, pp.1662~1669 (2010)
  15. Ciccocioppo, R, "Autologous bone marrow-derived mesenchymal stromal cells in the treatment of fistulising Crohn's disease", Gut, 60, pp.788~798 (2011)
  16. Le Blanc, K., "Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells", Lancet, 363, pp.1439~1441 (2004)
  17. Gu, Z, "Transplantation of umbilical cord mesenchymal stem cells alleviates lupus nephritis in MRL", lpr mice, 2010, pp.19, 1502~1514
  18. Ji, S., "Mesenchymal stem cell transplantation inhibits abnormal activation of Akt", GSK3beta signaling pathway in T cells from systemic lupus erythematosus mice, 2012, pp.29, 705~712
  19. Zhou, K, "Transplantation of human bone marrow mesenchymal stem cell ameliorates the autoimmune pathogenesis in MRL", lpr mice, 2008, pp.5, 417~424
  20. Youd, M., "Allogeneic mesenchymal stem cells do not protect NZBxNZW F1 mice from developing lupus disease", Clin. Exp. Immunol, 161, pp.176~186 (2010)
  21. Schena, F., "Interferon-gamma-dependent inhibition of B cell activation by bone marrow-derived mes enchymal stem cells in a murine model of systemic lupus erythematosus", Arthritis Rheum, 62, pp.2776~2786 (2010)
  22. Choi, E. W, "Reversal of serologic, immunologic, and histologic dysfunction in mice with systemic lupus erythematosus by long-term serial adipose tissue-derived mesenchymal stem cell transplantation", Arthritis Rheum, 64, pp.243~253 (2012)
  23. Firestein, G. S., "Evolving concepts of rheumatoid arthritis", Nature, 423, pp.356~361 (2003)
  24. Liu, Y, "Therapeutic potential of human umbilical cord mesenchymal stem cells in the treatment of rheumatoid arthritis", Arthritis Res. Ther, 12, pp.R210~ (2010)
  25. Zhou, B, "Administering human adipose-derived mesenchymal stem cells to prevent and treat experimental arthritis", Clin. Immunol, 141, pp.328~337 (2011)
  26. Augello, A, "Cell therapy using allogeneic bone marrow mesenchymal stem cells prevents tissue damage in collagen-induced arthritis", Arthritis Rheum, 56, pp.1175~1186 (2007)
  27. Papadopoulou, A., "Anagnostopoulos, and E. Yannaki. 2012. Mesenchymal stem cells are conditionally therapeutic in preclinical models of rheumatoid arthritis", Ann. Rheum. Dis, 71, pp.1733~1740 (2012)
  28. Gonzalez, M. A., "Adipose-derived mesenchymal stem cells alleviate experimental colitis by inhibiting inflammatory and autoimmune responses", Gastroenterology, 136, pp.978~989 (2009)
  29. Bouma, G., "The immunological and genetic basis of inflammatory bowel disease", Nat. Rev. Immunol, 3, pp.521~533 (2003)
  30. Akiyama, K., "Mesenchymalstem-cell-induced immunoregulation involves FAS-ligand-", FAS-mediated T cell apoptosis, 2012, pp.10, 544~555
  31. Zappia, E, "Mesenchymal stem cells ameliorate experimental autoimmune encephalomyelitis inducing T-cell anergy", Blood, 106, pp.1755~1761 (2005)
  32. Gerdoni, E., "Mesenchymal stem cells effectively modulate pathogenic immune response in experimental autoimmune encephalomyelitis", Ann. Neurol, 61, pp.219~227 (2007)
  33. Nauta, A. J, "Mesenchymal stem cells inhibit generation and function of both CD34+-derived and monocyte-derived dendritic cells", J. Immunol, 177, pp.2080~2087 (2006)
  34. Jiang, X. X, "Human mesenchymal stem cells inhibit differentiation and function of monocyte-derived dendritic cells", Blood, 105, pp.4120~4126 (2005)
  35. Aggarwal, S, "Human mesenchymal stem cells modulate allogeneic immune cell responses", Blood, 105, pp.1815~1822 (2005)
  36. Beyth, S, "Human mesenchymal stem cells alter antigen-presenting cell maturation and induce T-cell unresponsiveness", Blood, 105, pp.2214~2219 (2005)
  37. Maccario, R., "Interaction of human mesenchymal stem cells with cells involved in alloantigen-specific immune response favors the differentiation of CD4+ T-cell subsets expressing a regulatory", suppressive phenotype, 2005, pp.90, 516~525
  38. Zhang, W, "Effects of mesenchymal stem cells on differentiation, maturation, and function of human monocyte-derived dendritic cells", Stem Cells Dev, 13, pp.263~271 (2004)
  39. Chiesa, S, "Mesenchymal stem cells impair in vivo T-cell priming by dendritic cells", Proc. Natl. Acad. Sci. USA, 108, pp.17384~17389 (2011)
  40. Spaggiari, G. M., "MSCs inhibit monocyte-derived DC maturation and function by selectively interfering with the generation of immature DCs : central role of MSC-derived prostaglandin E2", Blood, 113, pp.6576~6583 (2009)
  41. Wehner, R., "Mesenchymal stem cells efficiently inhibit the proinflammatory properties of 6-sulfo LacNAc dendritic cells", Haematologica, 94, pp.1151~1156 (2009)
  42. Bartholomew, A., "Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo", Exp. Hematol, 30, pp.42~48 (2002)
  43. Krampera, M., "Bone marrow mesenchymal stem cells inhibit the response of naive and memory antigen-specific T cells to their cognate peptide", Blood, 101, pp.3722~3729 (2003)
  44. Maitra, B, "Human mesenchymal stem cells support unrelated donor hematopoietic stem cells and suppress T-cell activation", Bone Marrow Transplant, 33, pp.597~604 (2004)
  45. Gonzalez-Rey, E, "Human adipose-derived mesenchymal stem cells reduce inflammatory and T cell responses and induce regulatory T cells in vitro in rheumatoid arthritis", Ann. Rheum. Dis, 69, pp.241~248 (2010)
  46. Locatelli, F, "Mesenchymal stromal cells, from indifferent spectators to principal actors. Are we going to witness a revolution in the scenario of allograft and immune-mediated disorders?", Haematologica, 92, pp.872~877 (2007)
  47. Krampera, M, "Role for interferon-gamma in the immunomodulatory activity of human bone marrow mesenchymal stem cells", Stem Cells, 24, pp.386~398 (2006)
  48. Mougiakakos, D., "The impact of inflammatory licensing on heme oxygenase-1-mediated induction of regulatory T cells by human mesenchymal stem cells", Blood, 117, pp.4826~4835 (2011)
  49. Ren, G, "Inflammatory cytokine-induced intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in mesenchymal stem cells are critical for immunosuppression", J. Immunol, 184, pp.2321~2328 (2010)
  50. Corcione, A, "Human mesenchymal stem cells modulate B-cell functions", Blood, 107, pp.367~372 (2006)
  51. Tabera, S., "The effect of mesenchymal stem cells on the viability, proliferation and differentiation of B-lymphocytes", Haematologica, 93, pp.1301~1309 (2008)

관련 논문AI추천

이 간행물의 다른 논문 (6건)