Graft dysfunction in compassionate use of genetically engineered pig-to-human cardiac xenotransplantation: a case report

Mohiuddin, Muhammad M.; Singh, Avneesh K.; Scobie, Linda; Goerlich, Corbin E.; Grazioli, Alison; Saharia, Kapil; Crossan, Claire; Burke, Allen; Drachenberg, Cinthia; Oguz, Cihan; Lewis, Billeta; Hershfeld, Alena; Sentz, Faith; Tatarov, Ivan; Mudd, Sarah R.; Braileanu, Gheorghe; Rice, Kathryn; Paolini, John F.; Bondensgaard, Kent; Vaught, Todd D.; Kuravi, Kasinath; Sorrells, Lori; Dandro, Amy; Ayares, David; Lau, Christine L.; Griffith, Bartley P.

doi:10.1016/s0140-6736(23)00775-4

Cited by 75 publications

(43 citation statements)

References 32 publications

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“…The recently published case report of a genetically engineered pig‐to‐human cardiac xenotransplantation reported widespread endothelial injury, indicating antibody‐mediated rejection 22 . Nonetheless, respondents in our study were more concerned about the risks of infection than they were about the risk of rejection or unknown risks.…”

Section: Discussionmentioning

confidence: 54%

A study of knowledge and acceptance of kidney xenotransplantation among Chinese kidney transplant recipients and candidates

Tu,

Zhao,

Chen

et al. 2024

Xenotransplantation

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BackgroundIn recent years, the implementation of the first case of pig‐to‐human heart xenotransplantation and the report of three cases of pig‐to‐brain‐dead human recipient kidney transplantation indicate that xenotransplantation is getting closer to clinical application. In the near future, China may also launch clinical trials of kidney xenotransplantation. Therefore, it is necessary to investigate the level of knowledge and acceptance of xenotransplantation among kidney transplant recipients and candidates in China. This study aims to investigate the level of comprehension and acceptance of kidney xenotransplantation in kidney transplant recipients and explore related factors, providing a reference for promoting the application and clinical trials of xenotransplantation in the near future.MethodsA questionnaire was completed by 211 kidney transplant recipients and 21 candidates. Answers to the questionnaires were self‐administered by the respondents. Scores were compared using nonparametric tests, as well as using Chi‐square test or Fisher's exact test to compare differences in answers.ResultsRespondents demonstrated a high score of 75 (out of 100) on knowledge and acceptance of kidney xenotransplantation. The sector “Knowledge and Attitude” received the overall highest score from respondents (85.0 out of 100), while “Risks and Concerns” received the lowest score (50 out of 100). Interestingly, respondents paid more attention to infection risks but showed less concern about rejection or unknown risks. Furthermore, 191 respondents (82.3%) expected that pig kidney xenografts could function for at least 5 years or more. The scores were statistically significant in terms of age, gender, level of education, level of knowledge on the case of xenotransplantation clinical trial, and willingness to donate organs. cognitionConclusionsThe awareness rates of xenotransplantation are high among kidney transplant recipients and candidates, for which the majority showed a generally favorable attitude towards this procedure. Respondents did not have a comprehensive understanding of the specific knowledge of xenotransplantation and expressed more concern about the risk of infection compared to the risk of rejection and other unknown risks, while also expecting long‐term survival similar to allograft transplantation for pig kidney xenografts.

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Section: Discussionmentioning

confidence: 54%

A study of knowledge and acceptance of kidney xenotransplantation among Chinese kidney transplant recipients and candidates

Tu,

Zhao,

Chen

et al. 2024

Xenotransplantation

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“…A porcine heart with surplus human CD47 was given to an individual who did not qualify for allotransplantation and functioned for almost 7 weeks. 162 Species-specific viral pathogens could present a barrier to the process. 163 However, reasons why overabundance is preferable over natural amounts of membrane CD47 are wanting.…”

Section: 7mentioning

confidence: 99%

Tolerating CD47

Isenberg,

Montero

2024

Clinical & Translational Med

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Cluster of differentiation 47 (CD47) occupies the outer membrane of human cells, where it binds to soluble and cell surface receptors on the same and other cells, sculpting their topography and resulting in a pleiotropic receptor‐multiligand interaction network. It is a focus of drug development to temper and accentuate CD47‐driven immune cell liaisons, although consideration of on‐target CD47 effects remain neglected. And yet, a late clinical trial of a CD47‐blocking antibody was discontinued, existent trials were restrained, and development of CD47‐targeting agents halted by some pharmaceutical companies. At this point, if CD47 can be exploited for clinical advantage remains to be determined. Herein an airing is made of the seemingly conflicting actions of CD47 that reflect its position as a junction connecting receptors and signalling pathways that impact numerous human cell types. Prospects of CD47 boosting and blocking are considered along with potential therapeutic implications for autoimmune diseases and cancer.

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“…Novel insights have emerged from the first‐in‐man xenotransplantation cases since our last report 1 . A follow‐up study of the inaugural pig‐to‐human heart xenotransplantation at the University of Maryland (UMB) which was performed using enhanced immunosuppression including costimulation blockade, 2 showed (1) antibody‐mediated rejection, (2) inadvertent IVIG‐induced immune activation, (3) unexpected reactivation and replication of latent PCMV/PRV causing an inflammatory response, potentially all contributed to the eventual failure of the transplanted 10GE pig heart after two months 3 …”

Section: Studies In Manmentioning

confidence: 99%