Related Experiment Video
Updated: May 12, 2026
Depletion of Mouse Cells from Human Tumor Xenografts Significantly Improves Downstream Analysis of Target Cells
Published on: July 29, 2016
A data-driven analysis of patient selection for xenotransplant human clinical trials
Baris Ata1, Robert A Montgomery2, Yucel Naz Ozyoruk1
1The University of Chicago Booth School of Business, Chicago, Illinois, United States of America.
Abstract:
The demand for transplant organs far exceeds the available supply. In the United States alone, more than 90,000 patients are currently on the kidney transplant waitlist, yet only about one third of them will ever receive a transplant. Xenotransplantation, organ transplants from gene edited pigs, offers a potential solution to this shortage. Successful investigational transplants of pig kidneys into brain-dead recipients and expanded access cases involving living human recipients have resulted in the green-lighting of the first human clinical trials. Using the benchmark of 2-year survival of non-human primates in pre-clinical studies, we developed a tool that can identify individual wait-listed patients predicted to have a shorter life expectancy than with a xenotransplant, utilizing Random Survival Forest, DeepSurv and Cox Proportional-Hazards models. We found that it is hard to identify patients that reach clinical equipoise unless the expected xenograft survival exceeds two years, with the Random Survival Forest model identifying less than 5% of such patients. Few patients would benefit based on survival alone and potential beneficiaries are spread across more than 200 transplant centers. Several incentives could allow more patients to reach equipoise. At the same benchmark of 2-year xenograft survival, keeping patients inactive on the waitlist while they have a functioning xeno-kidney increases the percentage achieving equipoise by up to 1.7% across cohorts. Granting patients with failed xenografts the same priority as prior living donors increases this by up to 17.9%, while assigning them the highest priority raises it by up to 28.5%. We are able, however, to identify phenotypes that have a high mortality and low transplant rates in the current allocation system that could serve as acceptable candidates; while not achieving equipoise, they would enjoy the benefits of being dialysis free.
Insights
Xenotransplantation using gene-edited pig kidneys may solve organ shortages. A new tool identifies patients who could benefit, but few reach clinical equipoise based on survival alone. Incentives could expand eligibility for this life-saving therapy.
Area of Science:
- Transplantation immunology
- Bioengineering
- Medical informatics
Background:
- The critical shortage of human organs for transplantation necessitates alternative solutions.
- Xenotransplantation, using genetically modified animal organs, is a promising approach to address this demand.
- Recent advancements have led to the initiation of human clinical trials for pig kidney xenotransplantation.
Purpose of the Study:
- To develop a predictive tool for identifying kidney transplant wait-listed patients who would benefit from xenotransplantation.
- To assess the potential impact of various allocation strategies and patient management incentives on xenotransplantation eligibility.
Main Methods:
- Utilized Random Survival Forest, DeepSurv, and Cox Proportional-Hazards models to predict patient survival.
- Established a benchmark of 2-year non-human primate xenograft survival for pre-clinical assessment.
- Modeled the effects of different waitlist management strategies on patient equipoise.
Main Results:
- Identifying patients reaching clinical equipoise is challenging unless xenograft survival exceeds two years; Random Survival Forest identified <5% of such patients.
- Few patients benefit from xenotransplantation based on survival alone, with potential candidates dispersed across numerous centers.
- Incentives like maintaining waitlist status or prioritizing patients with failed xenografts could significantly increase the percentage of patients achieving equipoise.
Conclusions:
- While survival benefits alone limit the immediate pool of xenotransplantation candidates, specific patient phenotypes with high mortality and low transplant rates are identifiable.
- Policy and allocation adjustments, such as modified waitlist management and priority adjustments for xenograft recipients, are crucial for maximizing patient benefit.
- Xenotransplantation holds significant potential to alleviate organ shortages, but careful patient selection and strategic implementation are required to realize its full impact.
