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Updated: Sep 4, 2025
A Pre-Clinical Porcine Model of Orthotopic Heart Transplantation
Published on: April 27, 2019
Preclinical rationale and current pathways to support the first human clinical trials in cardiac xenotransplantation
Muhammad M Mohiuddin1, Avneesh K Singh1, Corbin E Goerlich1
1University of Maryland School of Medicine, Maryland, USA.
Abstract:
Recent initiation of the first FDA-approved cardiac xenotransplantation suggests xenotransplantation could soon become a therapeutic option for patients unable to undergo allotransplantation. Until xenotransplantation is widely applied in clinical practice, consideration of benefit versus risk and approaches to management of clinical xenografts will based at least in part on observations made in experimental xenotransplantation in non-human primates. Indeed, the decision to proceed with clinical trials reflects significant progress in last few years in experimental solid organ and cellular xenotransplantation. Our laboratory at the NIH and now at University of Maryland contributed to this progress, with heterotopic cardiac xenografts surviving more than two years and life-supporting cardiac xenografts survival up to 9 months. Here we describe our contributions to the understanding of the mechanism of cardiac xenograft rejection and development of methods to overcome past hurdles, and finally we share our opinion on the remaining barriers to clinical translation. We also discuss how the first in human xenotransplants might be performed, recipients managed, and graft function monitored.
Insights
Cardiac xenotransplantation shows promise as a therapy for patients ineligible for allotransplantation. Research in non-human primates advances understanding of xenograft rejection and clinical translation strategies.
Area of Science:
- Transplantation immunology
- Xenotransplantation research
- Medical innovation
Background:
- Cardiac xenotransplantation is emerging as a viable therapeutic option for patients with end-stage heart failure.
- Allotransplantation is limited by donor organ scarcity, necessitating alternative solutions.
- Experimental xenotransplantation in non-human primates is crucial for assessing clinical feasibility and safety.
Purpose of the Study:
- To review contributions to understanding cardiac xenograft rejection mechanisms.
- To highlight advancements in overcoming hurdles in xenotransplantation.
- To discuss future directions for clinical translation and patient management.
Main Methods:
- Utilizing non-human primate models for experimental cardiac xenotransplantation.
- Investigating mechanisms of xenograft rejection.
- Developing and evaluating strategies to prolong graft survival.
Main Results:
- Achieved heterotopic cardiac xenograft survival exceeding two years.
- Demonstrated life-supporting cardiac xenografts with survival up to nine months.
- Advanced understanding of xenograft rejection pathways.
Conclusions:
- Significant progress in experimental xenotransplantation supports clinical translation.
- Overcoming immunological barriers remains key for successful xenotransplantation.
- Careful consideration of risks, recipient management, and graft monitoring is essential for clinical xenografts.
