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
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)
Review
Medicine, General & Internal
David K. C. Cooper, Hidetaka Hara
Summary: Collaboration between the laboratory team and the clinical team is essential to prepare for the first clinical trial of life-supporting kidney transplantation in the genetically-engineered pig-to-nonhuman primate model. Determining optimal genetic modifications, immunosuppressive therapeutic regimens, and measures to minimize infectious risks are crucial for the progress of xenotransplantation.
Review
Immunology
Daniel L. Eisenson, Yu Hisadome, Kazuhiko Yamada
Summary: Organ transplantation is the most effective treatment for end stage organ failure, but there is a shortage of organs. Xenotransplantation using pig tissues is a potential solution to this issue. While gene editing has made significant progress, recent data suggests that it alone cannot overcome all immune barriers in xenotransplantation, necessitating active and innovative immunologic strategies.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Biology
Xuan Zhang, Quancheng Wang, Jingjun Zhao, Xiao Li, Wei Peng, Zhaoxu Yang, Zhibin Lin, Long Yang, Rui Ding, Kaishan Tao, Kefeng Dou
Summary: Organ shortage in allotransplantation is a major issue leading to patient deaths or transplant ineligibility. Genetically engineered pig organs have shown some progress as potential alternatives, but still face challenges such as rejection and inflammation. Further genetic modifications and pretransplant screenings are necessary for successful xenotransplantation.
SCIENCE CHINA-LIFE SCIENCES
(2021)
Review
Surgery
David K. C. Cooper, Richard N. Pierson III
Summary: Progress in pig organ xenotransplantation has been achieved by genetically modifying the organsource pig and using immunosuppressive therapy to suppress immune responses. These advancements have led to increased survival of pig organs and the successful performance of the first clinical pig heart transplant.
AMERICAN JOURNAL OF TRANSPLANTATION
(2023)
Article
Cardiac & Cardiovascular Systems
Ryan Chaban, David K. C. Cooper, Richard N. Pierson
Summary: The recent pig heart transplant at the University of Maryland Medical Center has sparked interest in xenotransplantation using genetically engineered pigs. By modifying pig genes and using immunosuppressive therapy, baboons have successfully survived with pig heart grafts for almost 9 months. The initial success suggests that pig hearts could be an effective bridge to allotransplantation, but their utility for destination therapy remains uncertain.
JOURNAL OF HEART AND LUNG TRANSPLANTATION
(2022)
Article
Biochemistry & Molecular Biology
Hien Lau, Shiri Li, Nicole Corrales, Samuel Rodriguez, Mohammadreza Mohammadi, Michael Alexander, Paul de Vos, Jonathan Lakey
Summary: Nec-1 supplementation has positive effects on both the in vitro and in vivo function of isolated PPIs, especially when added on day 3 of culture. It significantly improves islet recovery, proliferation and differentiation of endocrine cells. The use of Nec-1 can shorten time to normoglycemia, improve glycemic control, and increase circulating insulin levels.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Cardiac & Cardiovascular Systems
Bruno Reichart, David K. C. Cooper, Matthias Laengin, Ralf R. Toenjes, Richard N. Pierson, Eckhard Wolf
Summary: Heart transplantation is the most effective treatment for patients with terminal/advanced cardiac failure, but the limited availability of donor organs leads to high mortality rate on the waitlist. Mechanical assist devices are currently the only alternative, but their complication rate remains high. Pig heart xenotransplantation has emerged as a potential option, and this review discusses the concept, pathobiological aspects, and safety considerations of this approach. It also highlights the need for a regulatory and ethical framework for the safe clinical development of cardiac xenotransplantation.
CARDIOVASCULAR RESEARCH
(2023)
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)
Review
Immunology
Tiantian Lei, Lin Chen, Kejing Wang, Suya Du, Carmen Gonelle-Gispert, Yi Wang, Leo H. Buhler
Summary: Genetically modified pigs have the potential to address the shortage of human organ donors by overcoming species-specific barriers and reducing infection risk. Research focuses on the immunological mechanism of xenograft rejection and recent progress in preclinical and clinical studies, providing a promising foundation for pig-to-human xenotransplantation in the future.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Immunology
Lisha Mou, Guanghan Shi, David K. C. Cooper, Ying Lu, Jiao Chen, Shufang Zhu, Jing Deng, Yuanyuan Huang, Yong Ni, Yongqiang Zhan, Zhiming Cai, Zuhui Pu
Summary: Pig islet xenotransplantation shows promise as a treatment for type 1 diabetes. The optimal age of the pig donors and the immunological barrier are still being studied. Isolation of adult islets using GMP grade collagenase is effective, but neonatal islets have cost advantages. Genetic modification in pigs may prevent rejection, but its efficacy in islet transplantation needs further research.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Wenhao Wang, Jiansen Lu, Ying Song, Chun Zeng, Yongkui Wang, Cheng Yang, Bin Huang, Yifan Dai, Jian Yang, Liangxue Lai, Liping Wang, Daozhang Cai, Xiaochun Bai
Summary: In this study, GTKO pig cancellous bone showed advantages in repairing femoral condyle bone defects and inhibiting xenotransplant rejection. Compared with WT pig bone, GTKO pig bone had reduced heterologous immunogenicity, tightly integrated with the defect, and showed better osseointegration with an appropriate rate of resorption. Additionally, GTKO pig bone promoted new bone formation.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2022)
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)