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In Vitro and In Vivo Assessment of T, B and Myeloid Cells Suppressive Activity and Humoral Responses from Transplant Recipients
Published on: August 12, 2017
Nonhuman primate models of transplant tolerance: closer to the holy grail
William H Kitchens1, Andrew B Adams
1Emory Transplant Center, Atlanta, Georgia, USA.
Purpose Of Review:
Transplantation tolerance, successful acceptance of an organ without the perils of immunosuppression, has been a central goal of transplant research. Many strategies to achieve this tolerance have been examined over the past three decades, culminating in several human trials of transplant tolerance. This progression from the 'benchtop to the clinic' has depended on the successful implementation of these tolerance strategies in nonhuman primates. This review will examine the described methods of transplant tolerance induction in nonhuman primates.
Recent Findings:
Although costimulatory blockade and mixed chimerism have an established record of achieving transplant tolerance in nonhuman primates, some of the most innovative recent techniques of tolerance induction have relied on cellular transfer. This review will fully examine the role of regulatory T-cell transfer and the use of mesenchymal stem/stromal cells to promote tolerance of organ allografts in nonhuman primates.
Summary:
Use of translational nonhuman primate transplant models is a vital intermediate step to advance new approaches of transplant tolerance induction from the lab to the clinic. This review will explore numerous techniques of tolerance induction that have been piloted in primates, including depletional techniques, induction of mixed hematopoietic chimerism, costimulation blockade, and adoptive transfer of tolerogenic cell populations.
Insights
Achieving transplant tolerance in nonhuman primates is crucial for clinical success. This review explores innovative cellular transfer methods and established techniques like costimulatory blockade for organ acceptance without immunosuppression.
Area of Science:
- Transplantation immunology
- Regenerative medicine
Background:
- Transplant tolerance, the acceptance of transplanted organs without immunosuppression, is a major goal in transplantation.
- Nonhuman primate models are essential for translating tolerance strategies from the lab to clinical application.
Purpose of the Study:
- To review methods for inducing transplant tolerance in nonhuman primates.
- To examine the progression of tolerance strategies from preclinical research to human trials.
Main Methods:
- Review of published literature on transplant tolerance induction in nonhuman primates.
- Focus on cellular transfer techniques, including regulatory T-cell and mesenchymal stem/stromal cell transfer.
- Examination of established methods like costimulatory blockade and mixed chimerism.
Main Results:
- Costimulatory blockade and mixed chimerism are established methods for achieving transplant tolerance in nonhuman primates.
- Recent innovative techniques involve cellular transfer, specifically regulatory T-cells and mesenchymal stem/stromal cells.
- These cellular therapies show promise for promoting organ allograft tolerance.
Conclusions:
- Nonhuman primate models are vital for advancing transplant tolerance research.
- Numerous techniques, including depletional methods, mixed chimerism, costimulatory blockade, and adoptive cell transfer, have been piloted in primates.
- Successful translation of these strategies is key to achieving clinical transplant tolerance.
