The prospects for effectively using cell transplantation, tissue engineering, and organogenesis to replace organ function are diverse. Previous experiments in animals and humans have shown that stem cells can develop into muscle cells that are injected into the heart, enhancing cardiovascular function. Neither transplanted cells nor engineered tissue is suitable for replacing the function of a widely damaged heart. For this, allografts or xenografts are required.
Living donation is an incredibly altruistic way to save patients with organ failures: Donors can donate and save up to eight lives by donating their organs after death.
However, human organ transplantation and allograft present significant challenges, as the demand for the transplant far outstrips the availability of donor organs. Each year, less than a fourth of those on the transplant waiting list receive an organ transplant. Even if all potential donors choose to donate, human organ donations will continue to be in short supply. Around 20 individuals die in the United States every day while waiting for an organ transplant.
There are several factors behind the overcrowded waiting lists, from the increasing life expectancy of the population and rising obesity rates to the fact that even if patients are successful in receiving the transplants, they have long desired, most are not well equipped for transplantation due to poor general health, certain viral infections, or other medical problems.
Editing Animal Organs
The use of animal organs is a potential solution, but it is not easy to overcome the body's rejection of them. For example, the antigens on the surface of pig tissue are easily mixed and recognized, putting our immune system into attack mode. Drugs can help suppress the response, but this is simply incompetent. Biotechnology companies, leading with eGenesis in Massachusetts are therefore advancing gene editing techniques to modify animal tissue by removing these surface antigens molecules and immunoediting other genes to reduce the risk of cross-species infection and graft rejection.
The Genome Engineering and Production Platform operated by eGenesis gives an insight into how pigs’ organs help create an unlimited supply of organs. First, potential risks of viruses and diseases are eliminated by inactivating all endogenous retrovirus sequences within the porcine genome. On a macro level, biosecure’s animal production process also enables a transmission-free environment that inhibits pathogens’ growth and spread.
In addition, genomes are edited for a compatible organ specialized for human use. Multiplex Gene Editing addresses the many ways in which immune-mediated rejection of transplanted organs can occur, delivering a designated DNA sequence by precise Genetic integration that is site-directed, determining the qualities of the gene produced in the porcine cell and the exact location where the genetic payload is added, subtracted, or modified. As a result, unfavorable porcine genes might react poorly with the human immune system inactivated (Knock Outs) while human genes that render porcine cells identical immune identity are introduced (Gene Insertion) and reduce the likelihood of rejection from the host. These unique genetic alterations aim to minimize inflammation so that organs or cells are not recognized as foreign by the human immune system.
By editing pig DNA in this way, several biotech companies have now created animals with organs that are more compatible with the human body.
In the future, organ engineering may not require animals at all. Researchers are in the early stages of exploring how to design complex tissues from scratch. These include 3D-printed scaffolds in the shape of lungs, and generic 'organoids' grown from stem cells to mimic specific organs.
Although there are currently some hurdles, and others still to be discovered, we firmly believe that safe and reliable methods will be found to produce functional human organs or organ substitutes, all innovative ways to solve the organ shortage.
First pig-to-human heart transplant
In Baltimore, Maryland, the first patient to receive a transplanted heart from a genetically modified pig returns to daily trivial without any incompetence. However, critics and uncertainty suggest ethical and technical hurdles.
57-year-old David Bennett provided an opportunity for the team to proceed with research in xenotransplantation. Bennett had been in cardiac care for about two months and had been unable to acquire a mechanical heart pump due to an erratic heart pulse. He also couldn't have a human transplant since he had a history of not following physicians' treatment guidelines. Bennett would have died otherwise, so the team obtained FDA approval to implant a pig heart in him.
Though Bennett's treatment’s success is an opportunity for more to try similar procedures, ethicists will need to define what qualifies for a pig organ, according to Jeremy Chapman, a former transplant surgeon from the University of Sydney in Australia. According to him, the long wait for an organ is insufficient to warrant such a highly experimental and potentially harmful treatment. This is especially true for other organs, such as kidneys, because most individuals who are waiting for a kidney transplant can go with dialysis rather than a transplant.
Chapman compares the process to using experimental cancer treatments that are too hazardous to test on patients who have alternative options. He stated that ethicists would have to assess the odds of success against the hazards of keeping people waiting.
Ethics and the crowd
We question whether society, at least in the prevalent countries, is willing and able to bear what we consider to be the exorbitant cost of animal organs and 3D bioprinting for every patient who needs treatment, predicted 500,000 USD per surgery. Engrafting a personalized organ from animals would be much more expensive than an allogeneic organ transplant, even taking into account that ongoing immunosuppression may not be required. We suspect this question may lead to bringing down enthusiasm for xenotransplantation in the transplant community. For scientists, finally, addressing the ethical challenges of medical rationing and answering the ongoing supply shortages.
The science itself is also not convincing. The variations across species “preclude us moving further with that model to predict the clinical outcome”, according to Chapman, and so for Bennett’s case danger is still lurking around.
While the public hopes that advances in medicine and surgery would lead to new treatments and improved treatment of diseases that would reduce the need for organ transplants, “to do surgery on someone who doesn’t need it” is a big risk, said Dr. Anthony Atala, director of the Wake Forest Institute for Regenerative Medicine. Despoiling essential organs from donor exhibits potential risks as they age, and since organs such as kidneys may be transplanted from living donors to patients, ultimately the total amount of kidneys is fixed.
Whether ethics come in the way of providing organs in demand, people are desperate on the waiting list, and any alternatives bare the overwhelming pressure. In a decade or so, Frankenstein which seems to be fantasy and fiction may be found plausible and promising, starting with animal organs and 3D printing, and eventually organs on demand.
Reference:
“Our Approach: Producing Human-Compatible Organs.” EGenesis, https://egenesisbio.com/our-approach.
Regalado, Antonio. “Organs on Demand: 10 Breakthrough Technologies 2023.” MIT Technology Review, MIT Technology Review, 13 Jan. 2023, https://www.technologyreview.com/2023/01/09/1064867/engineered-organs-10-breakthrough-technologies-2023/.
Javelosa, June. “Organs on Demand: Bioprinting Will Be the Answer to Donor Shortages.” Futurism, Futurism, 25 Dec. 2016, https://futurism.com/neoscope/organs-on-demand-bioprinting-will-be-the-answer-to-donor-shortages.
Reardon, Sara. “First Pig-to-Human Heart Transplant: What Can Scientists Learn?” Nature News, Nature Publishing Group, 14 Jan. 2022, https://www.nature.com/articles/d41586-022-00111-9#:~:text=Last%20week%E2%80%99s%20procedure%20marks%20the%20first%20time%20that,legally%20dead%20people%20with%20no%20discernible%20brain%20function.