XENOTRANSPLANTATION PRESENTATION

Ruby Cockerton 12/05/23

The future of healthcare

Xenotransplantation

Conclusion

Progress

Challenges

Advantages

Introduction

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.

Norman Shumway

Xenotransplantation is the future, and always will be.

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.

Eliminates risk of human to human disease transmission

No shortage in availability of porcine organs

HUMAN DISEASE

PORCINE ORGANS

WAITING TIMES

Could prove essential in reducing time on the organ donor waitlist

Advantages

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/.

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.

Reduction in waiting times

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.

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

PORCINE ORGANS

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.

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.

ETHICAL ISSUES

Certain faiths and personal ethics reject the use of porcine organs

VIRUS RISK

The human immune system has no adaptation to porcine viruses

IMMUNE REJECTION

T-cell antibodies may be rejected by our immune systems

CHALLENGES

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.

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

IMMUNE REJECTION

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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PERV-A

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-B

VIRUS RISK

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ETHICAL ISSUES

agree with xenotransplantation

41.5%

41.5%

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?

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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PROGRESS TIMELINE

2022Bartley Griffith (USA)Pig heart60 days

1996Dhaniram Baruah (India)Pig heart7 days

1977Christian Barnard (South Africa)Chimpanzee heart4 days

1964James Hardy (USA)Chimpanzee heart90 minutes

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- Michael E. DeBakey

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

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?

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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?

THANKS FOR LISTENING!

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.‌‌‌‌‌‌‌‌‌

References