Engage! – Discussions on active involvement in personal health and global wellness.
Transplantation of vital organs including heart, lung, liver, kidney, and bone marrow tissue could be the only remaining option to save the life of a patient when other options of treatment have been exhausted. Bone marrow transplantation could be an effective treatment for several blood cancers, and in an India Currents article written in 2019, I speak of the urgent requirement for bone marrow donors within the Southeast Asian community as there is a dearth of sufficient marrow donors of Southeast Asian descent. Also mentioned are the registries and tissue banks that are available for bone marrow and stem cell donation in the US and internationally. While an appropriate match depends on the human leukocyte antigens (HLA) typing of donor samples and their compatibility with the patient receiving the transplant, the probability of finding a match increases within ethnic groups.
Two years onward this continues to be a problem, not only with bone marrow but with other organs as well, including the vital organs of the lung, liver, kidney, and heart. The Office of Minority Health of the US Health and Human Services provides telling data for 2020, where the number of total transplants performed in Asian Americans who were waiting for a transplant was approximately half of that performed on white Americans. In addition, while 8.5% of the total transplant candidates are Asians, they comprise only 3.1% of the pool of organ donors.
The best option for transplantation is a matched organ from a donor that is in an ideal condition to be functional in the patient. However, to stack the odds on the side of the patient waiting to receive an organ, several attempts are being made to increase the pool of transplantable organs. EVLP or ex-vivo lung perfusion is a technique where donor lungs which are discarded as being unusable as live organs can be rejuvenated by soaking in defined nutrients under defined conditions. Once they meet specific criteria, they are deemed ready for transplantation into patients.
3D bioprinting is an evolving technology where a scaffold of a matrix of the organ is printed (a simplistic comparison would be an ink-jet printer), usually with a stiff protein called collagen. In an alternative technology, discarded organs from humans or pigs may be decellularized carefully, where once all the cells have been removed one is left with the scaffold of the organ. Once the framework of the architecture of the organ is engineered in one way or another, the idea is that it can be populated with cells that constitute the organ. This is obviously more complex than it sounds, as all the vital organs have cell populations that live, die, and interact in specific harmonious ways to create a functional organ. However, the discovery of induced pluripotent stem cell (iPSC) technology can confer a double-powered boon for transplantation patients. Awarded the Nobel prize in 2012, this technology allows one to take mature cells from the recipient patient (say a skin sample) and take these cells back in time into a pluripotent state where they can now be coaxed to differentiate into practically any specialized cell of the body including cells of the heart, liver or other organs. In addition to now reducing the need for waiting for a donor organ, the success of this technology will make the use of immunosuppressants moot, as the transplanted organs will be a perfect match for the recipient patient since it is crafted from his/her own cells.
The idea of engineering biological life in a made-to-order fashion was perhaps exemplified by Aldous Huxley in 1932 in his novel Brave New World, where humans are bred artificially with a specific intention to preserve order in a dystopian world. However, the recent splash of news on January 10, 2022, created by the transplantation of an engineered pig heart into a 57-year-old man provides a potentially practical aspect to this idea. As against Huxley’s imagined world, in our real world, pigs are considered as an option to engineer and breed, with the objective of harvesting organs which may be a useful medical therapeutic option for human transplantation.
Transplantation across species is called xenotransplantation and, in this case, it was done under a ‘compassionate use’ authorization from the US Food and Drug Administration, a federal organization responsible for the protection of public health. The recipient was a patient who had end-stage heart disease and was not considered eligible for a human organ. The donor pigs were engineered such that their tissue would lead to a minimal immune reaction in a human host to tissue from another species, and to promote long-term survival of the organ in the patient. The similarity of the size of the pig heart to the human heart factors in the choice of pigs as a donor.
The success of this xenotransplantation that was attempted on a single patient remains to be seen, and learnings from this could play a role in the development of this therapeutic transplantation strategy. This pioneering attempt at xenotransplantation of an engineered organ brings up questions of ethical practices related to the intentional engineering of live organs, and also the regulated examination of the safety and efficacy of such transplantations with clinical trials.
Although several strategies are being explored for increasing the pool of transplantable and life-giving organs as described, at the present time it is important to consider organ donation as a primary source of a lease on life, for a patient with a failing vital organ.
L. Iyengar has lived and worked in India and the USA. A scientist by training, she enjoys experiencing diverse cultural ideas and writing. Her short story is featured in the anthology of international women writers ‘The Roots that Help Us Grow’ published in 2021 by The Nasiona. She can be found on Twitter at @l_iyengar.