Mesenchymal stem cells avoid allogeneic rejection

被引：646
作者：
Ryan J.M. [1 ]
Barry F.P. [2 ]
Murphy J.M. [2 ]
Mahon B.P. [1 ]
机构：
[1] Institute of Immunology, National University of Ireland, Maynooth, Co. Kildare
[2] Regenerative Medicine Institute (REMEDI), National Centre for Biomedical Engineering Science, National University of Ireland, Galway
来源：
Journal of Inflammation | / 2卷 / 1期
关键词：
Mesenchymal Stem Cell; Hepatocyte Growth Factor; Human Mesenchymal Stem Cell; Mixed Lymphocyte Reaction; Dendritic Cell Maturation;
D O I：
10.1186/1476-9255-2-8
中图分类号：
学科分类号：
摘要：
Adult bone marrow derived mesenchymal stem cells offer the potential to open a new frontier in medicine. Regenerative medicine aims to replace effete cells in a broad range of conditions associated with damaged cartilage, bone, muscle, tendon and ligament. However the normal process of immune rejection of mismatched allogeneic tissue would appear to prevent the realisation of such ambitions. In fact mesenchymal stem cells avoid allogeneic rejection in humans and in animal models. These finding are supported by in vitro co-culture studies. Three broad mechanisms contribute to this effect. Firstly, mesenchymal stem cells are hypoimmunogenic, often lacking MHC-II and costimulatory molecule expression. Secondly, these stem cells prevent T cell responses indirectly through modulation of dendritic cells and directly by disrupting NK as well as CD8+ and CD4+ T cell function. Thirdly, mesenchymal stem cells induce a suppressive local microenvironment through the production of prostaglandins and interleukin-10 as well as by the expression of indoleamine 2,3,-dioxygenase, which depletes the local milieu of tryptophan. Comparison is made to maternal tolerance of the fetal allograft, and contrasted with the immune evasion mechanisms of tumor cells. Mesenchymal stem cells are a highly regulated self-renewing population of cells with potent mechanisms to avoid allogeneic rejection. © 2005 Ryan et al; licensee BioMed Central Ltd.
引用
收藏
相关论文
共 112 条
  • [1] Mosca J.D., Hendricks J.K., Buyaner D., Davis-Sproul J., Chuang L.C., Majumdar M.K., Chopra R., Barry F., Murphy M., Thiede M.A., Junker U., Rigg R.J., Forestell S.P., Bohnlein E., Storb R., Sandmaier B.M., Mesenchymal stem cells as vehicles for gene delivery, Clin Orthop Relat Res, (2000)
  • [2] Barry F.P., Murphy J.M., Mesenchymal stem cells: Clinical applications and biological characterization, Int J Biochem Cell Biol, 36, pp. 568-584, (2004)
  • [3] Drukker M., Benvenisty N., The immunogenicity of human embryonic stem-derived cells, Trends Biotechnol, 22, pp. 136-141, (2004)
  • [4] Shizuru J.A., Negrin R.S., Weissman I.L., Hematopoietic stem and progenitor cells: Clinical and Preclinical Regeneration of the Hematolymphoid System, Annu Rev Med, 56, pp. 509-538, (2005)
  • [5] Pittenger M.F., Mackay A.M., Beck S.C., Jaiswal R.K., Douglas R., Mosca J.D., Moorman M.A., Simonetti D.W., Craig S., Marshak D.R., Multilineage potential of adult human mesenchymal stem cells, Science, 284, pp. 143-147, (1999)
  • [6] Friedenstein A.J.P., Petrokova K.V., Osteogenesis in transplants of bone marrow cells, Journal of Embyological Experimental Morphology, 16, pp. 381-390, (1966)
  • [7] Jiang Y., Jahagirdar B.N., Reinhardt R.L., Schwartz R.E., Keene C.D., Ortiz-Gonzalez X.R., Reyes M., Lenvik T., Lund T., Blackstad M., Du J., Aldrich S., Lisberg A., Low W.C., Largaespada D.A., Verfaillie C.M., Pluripotency of mesenchymal stem cells derived from adult marrow, Nature, 418, pp. 41-49, (2002)
  • [8] Reyes M., Verfaillie C.M., Characterization of multipotent adult progenitor cells, a subpopulation of mesenchymal stem cells, Ann N Y Acad Sci, 938, pp. 231-233, (2001)
  • [9] Jorgensen C., Gordeladze J., Noel D., Tissue engineering through autologous mesenchymal stem cells, Curr Opin Biotechnol, 15, pp. 406-410, (2004)
  • [10] Jorgensen C., Djouad F., Apparailly F., Noel D., Engineering mesenchymal stem cells for immunotherapy, Gene Ther, 10, pp. 928-931, (2003)
12345678910