Human mesenchymal stem cells and immunosuppressive drug interactions in allogeneic responses: an in vitro study using human cells

Transplant Proc. 2009 Oct;41(8):3347-52. doi: 10.1016/j.transproceed.2009.08.030.

Abstract

Objectives: The use of mesenchymal stem cells (MSC), which display immunosuppressive activity, seems to be a promising therapeutic approach in solid organ transplantation. However, little is known about their interactions with immunosuppressive drugs. The objective of this study was to assess these interactions in allogeneic responses.

Methods: We studied the effects on alloimmune responses in mixed lymphocyte reactions of MSC plus five agents-cyclosporine, tacrolimus, rapamycin, mycophenolate acid (MPA), and dexamethasone (DEX).

Results: Human MSC isolated from bone marrow were characterized by their phenotype and their ability to differentiate into adipocytes or osteoblastes. MSC plus the agents inhibited allogeneic lymphocyte proliferation in a dose-dependent manner. Calcineurin inhibitors and rapamycin antagonized the inhibitory effect of MSC, whereas MPA promoted it and DXM did not modify it.

Conclusion: MPA seems to be the best immunosuppressant to associated with MSC for transplanted patients.

MeSH terms

  • Adipocytes / drug effects
  • Adipocytes / immunology
  • Antigens, CD / immunology
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / drug effects
  • Bone Marrow Cells / immunology
  • Cell Differentiation
  • Cyclosporine / pharmacology
  • Dexamethasone / pharmacology
  • Flow Cytometry
  • Humans
  • Immunosuppressive Agents / pharmacology*
  • Lymphocytes / drug effects
  • Lymphocytes / immunology
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / immunology*
  • Mycophenolic Acid / pharmacology
  • Osteoblasts / drug effects
  • Osteoblasts / immunology
  • Sirolimus / pharmacology
  • Transplantation, Homologous / immunology*

Substances

  • Antigens, CD
  • Immunosuppressive Agents
  • Dexamethasone
  • Cyclosporine
  • Mycophenolic Acid
  • Sirolimus