REVIEW article
Front. Immunol.
Sec. Immunological Tolerance and Regulation
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1648926
Use of regulatory cells (RC) for achieving functional tolerance to pig heart xenotransplants in humans: a literature review
Provisionally accepted
- University of Maryland, Baltimore, United States
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Xenotransplantation of pig hearts may resolve the present human donor shortage after controlling for rejection. One innovative approach to combat rejection in humans may be the use of regulatory cells (RC) therapy. The term RC is used for all cell populations that have immunosuppressive functions in common. The use of RC, including mesenchymal stem cells (MSC) and CD4+CD125lowCD25highFoxp3+ T cells (Treg), may potentially eliminate chronic general immunosuppression (IS). This approach is hypothesized to act through the augmentation of suppressive immune mechanisms that maintain tolerance by prevailing over immune effector mechanisms of rejection. The increase of RC numbers by adoptive cell transfer (ACT) and improvement of their qualities by chimeric antigen receptor (CAR) technology are two promising strategies for RC therapy applications. During the different steps of rejection, monitoring specific biomarkers will indicate the use of a corresponding RC subpopulation, preferable available off-the-shelf, single or in combination, once or multiple times. In the future, exosomes or only RC derived active molecules (or their antagonists) may supplement or replace whole cell therapy. After more research RC therapy, not used in clinics yet to induce functional tolerance to pig heart xenotransplants in humans, has the potential to become a routine personalized treatment.
Keywords: pig heart xenotransplantation, regulatory cells therapy, adoptive cell transfer, xenotransplant tolerance, CAR transformed regulatory cells, human recipients, multianalyte biomarkers
Received: 17 Jun 2025; Accepted: 14 Oct 2025.
Copyright: © 2025 Braileanu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Gheorghe Braileanu, gbraileanu@som.umaryland.edu
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