XENOTRANSPLANTATION PRESENTATION

Ruby Cockerton 12/05/23

Xenotransplantation

The future of healthcare

Introduction

Advantages

Challenges

Progress

Conclusion

Introduction

Meier, R.P.H., Muller, Y.D., Balaphas, A., Morel, P., Pascual, M., Seebach, J.D. and Buhler, L.H. (2018). Xenotransplantation: back to the future? Transplant International, 31(5), pp.465–477. doi:https://doi.org/10.1111/tri.13104.

What is xenotransplantation?

Xenotransplantation is simply the process of moving tissues, cells, or organs from one species to another. This is a medical research field that is evolving rapidly as a solution for the organ shortage in humans, however there are many issues that come with xenotransplantation.

Xenotransplantation is the future, and always will be.

Norman Shumway

Advantages

HUMAN DISEASE

WAITING TIMES

PORCINE ORGANS

Could prove essential in reducing time on the organ donor waitlist

No shortage in availability of porcine organs

Eliminates risk of human to human disease transmission

Reduction in waiting times

As of 31st March 2023, there are 6948 people currently waiting for a transplant that could save their life. Between 2021-22 over 420 people died on the waiting list.

NHS (2022). Organ Donation and Transplantation. [online] NHS Blood and Transplant. Available at: https://www.nhsbt.nhs.uk/what-we-do/transplantation-services/organ-donation-and-transplantation/.

PORCINE ORGANS

• Unlimited availability
• Produce 5-12 offspring
• Grow to adult size within 6 months
• Pregnancy of 114+- 2 days

Cooper, D.K.C., Gaston, R., Eckhoff, D., Ladowski, J., Yamamoto, T., Wang, L., Iwase, H., Hara, H., Tector, M. and Tector, A.J. (2017). Xenotransplantation—the current status and prospects. British Medical Bulletin, [online] 125(1), pp.5–14. doi:https://doi.org/10.1093/bmb/ldx043.

HUMAN DISEASE

With human donor-to-recipient transplantation there is a risk of transmission of human diseases. Bone allografts have transmitted tuberculosis, hepatitis and HIV-1. Corneas have before transmitted rabies, CJD, HBV, CMV AND HSV.

Eastlund, T. (1995). Infectious disease transmission through cell, tissue, and organ transplantation: Reducing the risk through donor selection. Cell Transplantation, 4(5), pp.455–477. doi:https://doi.org/10.1016/0963-6897(95)00035-v.

CHALLENGES

IMMUNE REJECTION

VIRUS RISK

ETHICAL ISSUES

Certain faiths and personal ethics reject the use of porcine organs

The human immune system has no adaptation to porcine viruses

T-cell antibodies may be rejected by our immune systems

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Griffith, B.P., Goerlich, C.E., Singh, A.K., Rothblatt, M., Lau, C.L., Shah, A., Lorber, M., Grazioli, A., Saharia, K.K., Hong, S.N., Joseph, S.M., Ayares, D. and Mohiuddin, M.M. (2022). Genetically Modified Porcine-to-Human Cardiac Xenotransplantation. New England Journal of Medicine. doi:https://doi.org/10.1056/nejmoa2201422.

IMMUNE REJECTION

Galactose α-l,3-galactose (GAL) -> α1,3-galactosyltransferase gene-knockout (GTKO) CRPs, CD (CD55 and CD59), 46 membrane cofactor proteins added to GAL Inhibits T-cell mediated rejection

Cooper, D.K.C., Ekser, B. and Tector, A.J. (2015). IMMUNOBIOLOGICAL BARRIERS TO XENOTRANSPLANTATION. International journal of surgery (London, England), [online] 23(0 0), pp.211–216. doi:https://doi.org/10.1016/j.ijsu.2015.06.068.

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VIRUS RISK

PERV are present in the genomes of all pigs, and cannot be removed through pathogen-free breeding. Swine viruses could infect human cells, grow and mutate, form new viruses and even cause a new pandemic. e.g. bird flu, ebola

PERV-A

PERV-B

dora.missouri.edu. (n.d.). Guinea pig Cytomegalovirus (GpCMV). [online] Available at: https://dora.missouri.edu/guinea-pig/guinea-pig-cytomegalovirus-gpcmv/.Senthilingam, M. (2015). The worms that invade your brain. [online] CNN. Available at: https://edition.cnn.com/2015/01/20/health/tapeworms-invade-brain/index.html [Accessed 14 Apr. 2023].Alam, A.M. (2022). Nipah virus, an emerging zoonotic disease causing fatal encephalitis. Clinical Medicine, pp.clinmed.2022-0166. doi:https://doi.org/10.7861/clinmed.2022-0166.

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ETHICAL ISSUES

41.5%

agree with xenotransplantation

Religious concerns arise in the Jewish and Islamic faiths. These have forbidden the use of pigs. Dhaniram Baruah was sentenced to 40 days in prison. His townspeople shunned him, and his farm and lab were destroyed. Vegetarianism and veganism?

41.5%

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PROGRESS TIMELINE

2022Bartley Griffith (USA) Pig heart 60 days

1977Christian Barnard (South Africa)Chimpanzee heart 4 days

1964James Hardy (USA) Chimpanzee heart 90 minutes

1996Dhaniram Baruah (India) Pig heart 7 days

Wadiwala, I.J., Garg, P., Yazji, J.H., Alamouti-fard, E., Alomari, M., Hussain, M.W.A., Elawady, M.S. and Jacob, S. (2022). Evolution of Xenotransplantation as an Alternative to Shortage of Donors in Heart Transplantation. Cureus, [online] 14(6). doi:https://doi.org/10.7759/cureus.26284.

Columbia University Irving Medical Center. (2022). How Close Is Xenotransplantation, Really? [online] Available at: https://www.cuimc.columbia.edu/news/how-close-xenotransplantation-really [Accessed 14 Apr. 2023].

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CONCLUSION

How severe is the problem with the organ donor waiting list? Do the benefits of xenotransplantation outweight the issues? How much future research needs to be done before porcine xenotransplantation is ready to be used on the public?

Xenotransplantation offers the promise of saving lives, but it also poses some of the greatest ethical and medical challenges of our time

- Michael E. DeBakey

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THANKS FOR LISTENING!

How does the public reconcile our ethical concerns about using animals as organ donors if porcine xenotransplantation proves to be a solution to save human lives?

References

Meier, R.P.H., Muller, Y.D., Balaphas, A., Morel, P., Pascual, M., Seebach, J.D. and Buhler, L.H. (2018). Xenotransplantation: back to the future? Transplant International, 31(5), pp.465–477. doi:https://doi.org/10.1111/tri.13104. Cooper, D.K.C., Gaston, R., Eckhoff, D., Ladowski, J., Yamamoto, T., Wang, L., Iwase, H., Hara, H., Tector, M. and Tector, A.J. (2017). Xenotransplantation—the current status and prospects. British Medical Bulletin, [online] 125(1), pp.5–14. doi:https://doi.org/10.1093/bmb/ldx043. Cooper, D.K.C., Ekser, B. and Tector, A.J. (2015). IMMUNOBIOLOGICAL BARRIERS TO XENOTRANSPLANTATION. International journal of surgery (London, England), [online] 23(0 0), pp.211–216. doi:https://doi.org/10.1016/j.ijsu.2015.06.068. Columbia University Irving Medical Center. (2022). How Close Is Xenotransplantation, Really? [online] Available at: https://www.cuimc.columbia.edu/news/how-close-xenotransplantation-really [Accessed 14 Apr. 2023]. NHS (2022). Organ Donation and Transplantation. [online] NHS Blood and Transplant. Available at: https://www.nhsbt.nhs.uk/what-we-do/transplantation-services/organ-donation-and-transplantation/. Wadiwala, I.J., Garg, P., Yazji, J.H., Alamouti-fard, E., Alomari, M., Hussain, M.W.A., Elawady, M.S. and Jacob, S. (2022). Evolution of Xenotransplantation as an Alternative to Shortage of Donors in Heart Transplantation. Cureus, [online] 14(6). doi:https://doi.org/10.7759/cureus.26284. Eastlund, T. (1995). Infectious disease transmission through cell, tissue, and organ transplantation: Reducing the risk through donor selection. Cell Transplantation, 4(5), pp.455–477. doi:https://doi.org/10.1016/0963-6897(95)00035-v. Griffith, B.P., Goerlich, C.E., Singh, A.K., Rothblatt, M., Lau, C.L., Shah, A., Lorber, M., Grazioli, A., Saharia, K.K., Hong, S.N., Joseph, S.M., Ayares, D. and Mohiuddin, M.M. (2022). Genetically Modified Porcine-to-Human Cardiac Xenotransplantation. New England Journal of Medicine. doi:https://doi.org/10.1056/nejmoa2201422. Soares, C., Hong-Zohlman, S.N., Hong, C.C., Goerlich, C.E., Benitez, R.M., Dickfeld, T., Gupta, A., Grazioli, A., Joseph, S., Mohiuddin, M., Griffith, B.P. and Ananthram, M. (2023). CORRELATION OF LV -GLOBAL LONGITUDINAL STRAIN WITH INVASIVE HEMODYNAMICS IN THE FIRST GENETICALLY MODIFIED PORCINE TO HUMAN XENO TRANSPLANT. Journal of the American College of Cardiology, 81(8), p.676. doi:https://doi.org/10.1016/s0735-1097(23)01120-8. dora.missouri.edu. (n.d.). Guinea pig Cytomegalovirus (GpCMV). [online] Available at: https://dora.missouri.edu/guinea-pig/guinea-pig-cytomegalovirus-gpcmv/. Senthilingam, M. (2015). The worms that invade your brain. [online] CNN. Available at: https://edition.cnn.com/2015/01/20/health/tapeworms-invade-brain/index.html [Accessed 14 Apr. 2023]. Alam, A.M. (2022). Nipah virus, an emerging zoonotic disease causing fatal encephalitis. Clinical Medicine, pp.clinmed.2022-0166. doi:https://doi.org/10.7861/clinmed.2022-0166. ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌ ‌