Review
Immunology
Manuel Alfredo Podesta, Megan Sykes
Summary: The induction of transplantation tolerance through hematopoietic cell transplantation has successfully achieved immune tolerance to kidney allografts from living donors in humans, which could potentially overcome the negative effects of chronic rejection and immunosuppression-related toxicity on long-term outcomes of kidney transplantation. Studies in animal models and humans have elucidated different mechanisms underlying tolerance induction, highlighting the importance of donor chimerism and Treg-mediated suppression for achieving immune tolerance in kidney transplantation.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Immunology
Shiva Pathak, Everett H. Meyer
Summary: Pancreatic islet transplantation is a promising method for treating diabetes, but long-term use of immunosuppressive drugs is crucial for islet graft survival. Current ISD regimens have significant side effects, and preclinical studies suggest that using T-regs and hematopoietic mixed chimerism may be the most promising strategies for inducing immune tolerance.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Thomas Fehr, Kerstin Huebel, Olivier de Rougemont, Irene Abela, Ariana Gaspert, Tayfun Guengoer, Mathias Hauri, Birgit Helmchen, Claudia Linsenmeier, Thomas Mueller, Jakob Nilsson, Oliver Riesterer, John D. Scandling, Urs Schanz, Pietro E. Cippa
Summary: This study reports the first European clinical trial on kidney transplantation aiming to induce immunological tolerance through mixed lymphohematopoietic chimerism. The results demonstrate that combined kidney and hematopoietic stem cell transplantation from an HLA-matched sibling is a feasible and successful approach, while maintaining immune responsiveness to mRNA vaccines.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Hongfeng Huang, Qixia Shen, Jingyi Zhou, Xiuyan Yang, Qiuqin Cai, Jia Shen, Shi Feng, Wenqing Xie, Hong Jiang, Jianghua Chen
Summary: The clinical experience demonstrates the efficacy of non-myeloablative conditioning protocol in inducing tolerance in HLA identical patients, and complete chimerism may be a risk factor for GVHD.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Wensheng Zhang, Yong Wang, Fushun Zhong, Xinghuan Wang, Robert Sucher, Cheng-Hung Lin, Gerald Brandacher, Mario G. G. Solari, Vijay S. S. Gorantla, Xin Xiao Zheng
Summary: In this study, using rodent vascularized composite allotransplantation (VCA) models, it was demonstrated that the presence of donor-derived hematopoietic stem cell (HSC) niches in vascularized bone components facilitates long-term hematopoietic chimerism and promotes tolerance in recipients without harsh myeloablation. The transplanted donor HSC niches also contribute to the maintenance and homeostasis of stable mixed chimerism. Additionally, evidence was provided that chimeric thymus plays a role in the tolerance induced by mixed chimerism through thymic central deletion. This study suggests the potential use of vascularized donor bone with pre-engrafted HSC niches as a safe and effective strategy to induce robust and stable mixed chimerism-mediated tolerance in vascularized composite allotransplantation or solid organ transplantation recipients.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Alexandre G. Lellouch, Alec R. Andrews, Gaelle Saviane, Zhi Yang Ng, Ilse M. Schol, Marion Goutard, Amon-Ra Gama, Ivy A. Rosales, Robert B. Colvin, Laurent A. Lantieri, Mark A. Randolph, Gilles Benichou, Curtis L. Cetrulo Jr
Summary: A new adapted conditioning protocol has been developed to achieve tolerance across MHC class-I-mismatched barriers in pigs, demonstrating the first successful mixed chimerism-induced VCA tolerance in a large animal model.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Immunology
Min Hu, Natasha M. Rogers, Jennifer Li, Geoff Y. Zhang, Yuan Min Wang, Karli Shaw, Philip J. O'Connell, Stephen Alexander
Summary: Tregs play a crucial role in kidney transplantation by limiting immune activation and potentially reducing the need for immunosuppression. Studies have shown their importance in improving allo-specific Treg function in both animal and human models.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Immunology
Abraham J. Matar, David H. Sachs, Raimon Duran-Struuck
Summary: The specialized herd of miniature swine homozygous for the swine major histocompatibility complex (MHC), known as MHC-characterized miniature swine (Mc-MS), has played a crucial role in transplantation research over the past 40 years. They have been used for studying surgical techniques, tolerance induction, and immunobiology of allografts and xenografts. The advantageous characteristics of Mc-MS make them an important tool in bridging the gap between laboratory and clinical applications in transplantation.
Article
Surgery
Dixon B. Kaufman, Lisa J. Forrest, John Fechner, Jennifer Post, Jennifer Coonen, Lynn D. Haynes, W. John Haynes, Neil Christensen, Weixiong Zhong, Christopher J. Little, Anthony D'Alessandro, Luis Fernandez, Kevin Brunner, Kent Jensen, William J. Burlingham, Peiman Hematti, Samuel Strober
Summary: This study describes the development of a novel post-transplant kidney transplant tolerance induction protocol in a rhesus macaque model using a total lymphoid irradiation (TLI) conditioning method. The protocol involved achieving a mixed chimeric state by infusing donor hematopoietic cells (HC) using TomoTherapy TLI, with the goal of eliminating immunosuppressive medications while maintaining allograft function long-term. Two out of eleven renal transplant recipients in the experimental group achieved mixed chimerism and operational tolerance, maintaining normal renal allograft function for 4 years without rejection or graft-versus-host disease (GVHD). None of the animals in the control group achieved tolerance when immunosuppressive medications were eliminated.
TRANSPLANT INTERNATIONAL
(2023)
Article
Medicine, General & Internal
Rainer Oberbauer, Matthias Edinger, Gabriela Berlakovich, Peter Kalhs, Nina Worel, Georg Heinze, Michael Wolzt, Thomas Lion, Thomas Wekerle
Summary: This study aims to investigate whether treatment with recipient Tregs and donor BM can lead to transient chimerism in kidney transplant recipients, potentially offering a new therapeutic option for immunomodulation in organ transplantation.
FRONTIERS IN MEDICINE
(2021)
Article
Surgery
Tomoki Murata, Naoki Hama, Tomoki Kamatani, Akihiro Mori, Ryo Otsuka, Haruka Wada, Ken-ichiro Seino
Summary: This study investigated the immune regulation in transplantation using allogeneic induced pluripotent stem cells (iPSCs). The researchers found that minor antigen mismatches are a risk factor for graft rejection, highlighting the importance of immune regulation. They demonstrated that iPSC-derived hematopoietic stem/progenitor cells (iHSPCs) can induce allograft tolerance, providing a new approach for transplantation.
AMERICAN JOURNAL OF TRANSPLANTATION
(2023)
Article
Medical Laboratory Technology
Linnea Pettersson, Francesco Vezzi, Sofie Vonlanthen, Karin Alwegren, Anders Hedrum, Dan Hauzenberger
Summary: This study aimed to evaluate a novel NGS-based assay for monitoring mixed chimerism, and found that NGS demonstrated high sensitivity and good accuracy, outperforming real-time PCR and fragment analysis techniques.
CLINICA CHIMICA ACTA
(2021)
Article
Cell Biology
Hajime Sasaki, Takayuki Hirose, Tetsu Oura, Ryo Otsuka, Ivy Rosales, David Ma, Grace Lassiter, Ahmad Karadagi, Toshihide Tomosugi, Abbas Dehnadi, Masatoshi Matsunami, Susan Raju Paul, Patrick M. Reeves, Isabel Hanekamp, Samuel Schwartz, Robert B. Colvin, Hang Lee, Thomas R. Spitzer, A. Benedict Cosimi, Pietro E. Cippa, Thomas Fehr, Tatsuo Kawai
Summary: Hematopoietic stem cell transplantation (HSCT) has potential applications beyond current standard indications. Selective inhibition of B cell lymphoma 2 (Bcl-2) shows promise in promoting hematopoietic chimerism without myelosuppression and making HSCT more feasible for a variety of clinical indications.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Review
Immunology
Jason Cheung, Beata Zahorowska, Michael Suranyi, Jeffrey K. W. Wong, Jason Diep, Stephen T. T. Spicer, Nirupama D. D. Verma, Suzanne J. Hodgkinson, Bruce M. M. Hall
Summary: The immune response to an allograft can activate lymphocytes that cause rejection. The activation of T regulatory cells can reduce allograft rejection and induce immune tolerance. Activated T regulatory cells can be distinguished by various markers. A more detailed characterization of these cells may help reduce non-specific immunosuppression.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Leo Ruhnke, Friedrich Stoelzel, Uta Oelschlaegel, Malte von Bonin, Katja Sockel, Jan Moritz Middeke, Christoph Roellig, Korinna Joehrens, Johannes Schetelig, Christian Thiede, Martin Bornhaeuser
Summary: This study reports the first case series of long-term survivors with mixed donor chimerism (MC) and finds an association between MC and increased CD4(+)/FOXP3(+) cells in bone marrow. The results suggest that reduced-intensity conditioning (RIC) and T cell depletion may be linked to MC, CD34(+) MC could be a potential predictor of relapse, CD4(+) MC may be associated with reduced risk of GVHD, and T-regs may play a role in maintaining immune tolerance post-HCT.
FRONTIERS IN ONCOLOGY
(2021)