Mesenchymal stem cells modulate immune responses combined with cyclosporine in a rat renal transplantation model

W Zhang1, C Qin, Z M Zhou

  • 1Key Lab of Reproductive Medicine of Jiang Su Province, Nanjing Medical University, and Department of Urology, First Affiliated Hospital of Nanjing Medical University, People's Republic of China.

Transplantation Proceedings
|December 20, 2007
PubMed

Insights

Mesenchymal stem cells (MSCs) show potential in down-regulating immune responses and preserving graft function. While not as potent as cyclosporine (CsA), MSCs may allow for reduced CsA doses when used in combination therapy.

Area of Science:

  • Immunology
  • Regenerative Medicine
  • Transplantation Biology

Background:

  • Mesenchymal stem cells (MSCs) are multipotent stromal cells with immunomodulatory properties.
  • The in vivo immunomodulatory effects of MSCs are hypothesized but require experimental substantiation.
  • Understanding MSCs' impact on immune responses is crucial for optimizing transplantation outcomes.

Purpose of the Study:

  • To investigate the immunomodulatory effects of MSCs in a transplantation model.
  • To evaluate the impact of MSCs on graft function, survival, and inflammatory mediator production.
  • To explore the potential synergistic or interactive effects of MSCs combined with cyclosporine (CsA).

Main Methods:

  • Graft function and histology were assessed post-transplantation.
  • Animal survival was monitored.
  • Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to analyze gene expression of inflammatory mediators, including interleukin (IL)-1, tumor necrosis factor (TNF)-alpha, and transforming growth factor (TGF)-beta1.
  • Comparisons were made between MSC therapy, CsA monotherapy, and combination therapy.

Main Results:

  • MSCs demonstrated a capacity to down-regulate immune responses and reduce inflammatory mediator production.
  • MSC treatment preserved initial graft function and prolonged animal survival.
  • The therapeutic effects of MSCs were less pronounced than those of CsA monotherapy.
  • Combination therapy with MSCs and low-dose CsA preserved graft function but did not extend survival beyond CsA monotherapy.

Conclusions:

  • MSCs possess immunomodulatory capabilities that benefit graft survival and function in the early post-transplantation period.
  • MSC therapy offers a potential adjunct to immunosuppressive drugs like CsA.
  • The findings suggest an interaction between MSCs and CsA, potentially enabling the use of lower CsA dosages.
  • Further research is warranted to elucidate the mechanisms underlying MSC-CsA interactions and optimize combination therapies.