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Mesenchymal Stromal Cell Therapy in Solid Organ Transplantation
Manuel Alfredo Podestà1, Giuseppe Remuzzi2, Federica Casiraghi2
1Department of Health Sciences, Università degli Studi di Milano, Milan, Italy.
Abstract:
Transplantation is the gold-standard treatment for the failure of several solid organs, including the kidneys, liver, heart, lung and small bowel. The use of tailored immunosuppressive agents has improved graft and patient survival remarkably in early post-transplant stages, but long-term outcomes are frequently unsatisfactory due to the development of chronic graft rejection, which ultimately leads to transplant failure. Moreover, prolonged immunosuppression entails severe side effects that severely impact patient survival and quality of life. The achievement of tolerance, i.e., stable graft function without the need for immunosuppression, is considered the Holy Grail of the field of solid organ transplantation. However, spontaneous tolerance in solid allograft recipients is a rare and unpredictable event. Several strategies that include peri-transplant administration of non-hematopoietic immunomodulatory cells can safely and effectively induce tolerance in pre-clinical models of solid organ transplantation. Mesenchymal stromal cells (MSC), non-hematopoietic cells that can be obtained from several adult and fetal tissues, are among the most promising candidates. In this review, we will focus on current pre-clinical evidence of the immunomodulatory effect of MSC in solid organ transplantation, and discuss the available evidence of their safety and efficacy in clinical trials.
Insights
Achieving stable graft function without immunosuppression, known as tolerance, is crucial for solid organ transplantation. Mesenchymal stromal cells (MSC) show promise in pre-clinical models for inducing this tolerance, potentially improving long-term transplant outcomes.
Area of Science:
- Immunology
- Transplantation Medicine
- Regenerative Medicine
Background:
- Solid organ transplantation is a life-saving treatment for organ failure.
- Current immunosuppressive therapies improve short-term survival but lead to chronic rejection and severe side effects.
- Achieving stable graft function without immunosuppression (tolerance) remains a major goal.
Purpose of the Study:
- To review pre-clinical evidence on the immunomodulatory effects of mesenchymal stromal cells (MSC) in solid organ transplantation.
- To discuss the safety and efficacy of MSC in ongoing clinical trials for transplantation.
Main Methods:
- Review of pre-clinical studies investigating MSC-mediated immunomodulation in solid organ transplant models.
- Analysis of clinical trial data assessing MSC safety and efficacy in transplant recipients.
Main Results:
- Pre-clinical data suggest MSC can safely and effectively induce tolerance in solid organ transplantation models.
- MSC demonstrate significant immunomodulatory effects relevant to preventing graft rejection.
- Early clinical evidence indicates potential safety and efficacy of MSC in transplant patients.
Conclusions:
- Mesenchymal stromal cells are a promising cell-based therapy for inducing immune tolerance in solid organ transplantation.
- Further clinical investigation is warranted to establish MSC as a standard treatment to improve long-term transplant outcomes and reduce immunosuppression-related complications.
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