1. Department of Cardiac Surgery, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100032, China
2. State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100032, China
3. Beijing Key Laboratory of Organ Xenotransplantation, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100032, China
4. Department of Cardiac Surgery, Fuwai Yunnan Hospital, Chinese Academy of Medical Sciences, Affiliated Cardiovascular Hospital of Kunming Medical University, Kunming, China
5. Shenzhen Key Laboratory of Cardiovascular Disease, Fuwai Hospital, Chinese Academy of Medical Sciences, Shenzhen, China
6. Sanya Institute of China Agricultural University, Sanya, China
Corresponding author:
fwsongjiangping@126.com
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History+
Received
Accepted
Published Online
2025-11-21
2026-04-29
2026-09-18
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Abstract
Cardiac xenotransplantation offers a potential solution to the persistent donor heart shortage. Yet durable graft survival remains elusive due to interconnected biological barriers. This review summarizes recent advances and persistent challenges in pig-to-human cardiac xenotransplantation, focusing on how integrated strategies—spanning donor engineering, perioperative care, and systems-level pathophysiology—may improve long-term graft function. Key barriers include immune rejection, coagulation dysregulation, graft hypertrophy, metabolic incompatibility, instability of transgene expression, endothelial injury, and biosafety risks. Critically, xenograft failure reflects a systems-level interplay of immune, coagulative, metabolic, vascular, growth-related, and infectious mechanisms rather than isolated defects. We highlight integrated approaches, particularly advanced donor engineering combined with perioperative support, targeted immunomodulation, growth control, organ preservation, ex vivo perfusion, metabolic support, and biosafety governance, that are reshaping clinical feasibility.
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