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Use of Brain Death Recipients in Xenotransplantation: A Double-Edged Sword
Xingchao Du1,2, Yuan Chang1,2, Jiangping Song1,2,3
1Beijing Key Laboratory of Preclinical Research and Evaluation for Cardiovascular Implant Materials, Animal Experimental Centre, National Centre for Cardiovascular Disease, Department of Cardiac Surgery, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Abstract:
Organ transplants are used to treat many end-stage diseases, but a shortage of donors means many patients cannot be treated. Xenogeneic organs have become an important part of filling the donor gap. Many current studies of kidney, heart, and liver xenotransplantation have used gene-edited pig organs on brain-dead recipients. However, the endocrine system, immune system, and nervous system of brain-dead people are changed, which are different from that of real patients transplanted, and the current research results of brain death (BD) recipients are also different. So there are drawbacks to using brain-dead people for xenotransplantation. In addition, although the policy requires the use of non-human primate (NHP) experiments as the research standard for xenotransplantation, there are still differences between NHP and humans in terms of immunity. Therefore, to better study xenotransplantation, new models may be needed in addition to NHP and brain-dead individuals. Humanized animal models or organoids may be able to fill this gap.
Insights
Xenotransplantation using gene-edited pig organs faces challenges with current models like brain-dead recipients and non-human primates. New models, such as humanized animals or organoids, are needed for better xenotransplantation research.
Area of Science:
- Transplantation immunology
- Regenerative medicine
- Surgical innovation
Background:
- Organ transplantation is vital for end-stage diseases but faces donor shortages.
- Xenotransplantation, using animal organs, offers a potential solution to the donor gap.
- Current research often uses gene-edited pig organs in brain-dead recipients or non-human primates (NHPs).
Purpose of the Study:
- To evaluate the limitations of current models in xenotransplantation research.
- To identify the need for improved preclinical models for xenotransplantation.
- To explore alternative models for advancing xenotransplantation studies.
Main Methods:
- Review of current xenotransplantation research methodologies.
- Analysis of physiological differences between brain-dead individuals, NHPs, and human patients.
- Identification of limitations in existing animal models for xenotransplantation.
Main Results:
- Brain-dead recipients exhibit altered physiological states, differing from actual transplant patients.
- Non-human primates, while a standard, possess immune differences compared to humans.
- Existing models may not fully replicate the human response to xenotransplantation.
Conclusions:
- Brain-dead individuals and NHPs present significant limitations as models for xenotransplantation.
- Humanized animal models and organoids show promise as superior alternatives.
- Development of novel, more accurate models is crucial for advancing xenotransplantation efficacy and safety.
