Organ Transplantation: Bioartificial Organs as The Future

Despite many possible life-concerning consequences following an allogeneic organ transplantation such as graft rejection, side effects from long-term immunosuppression and unquantifiable risk of disease transmissions, many patients with organ failures are still currently in desperate need for a new, healthy organ to have a second chance at life. Therefore this essay will discuss bioartificial organs as the future of organ transplantation.

The Ott Laboratory for Organ engineering and regeneration has taken a lead in the regenerative medicine and biotechnology industries by suggesting a method that minimizes the risk of rejections and the need for immunosuppression following an organ transplantation. Dr. Harald Ott, the founder of the company, had the idea of infusing patient-specific, differentiated cells from human pluripotent stem cells into decellularized donor organ scaffolds, generating an ‘personalized’ organ for transplantation. The new bioartificial organ will then be placed in a bioreactor, where it will sit until full maturation, and finally be implanted into the patient.

Despite it being at its initial development stage, many successful experiments on smaller animals have shown this technology to be applicable as an alternate source for organ transplantation. Firstly, experiments on RNU rats have shown that engineered bioartificial intestines can regain basic and life-sustaining functionalities, such as ‘up taking glucose and fatty acids in vivo. Secondly, Dr. Ott and his team’s bioengineered kidney was shown to partially restore basic physiological functionality of a native kidney such as macromolecular sieving, glucose and electrolyte reabsorption. The successes from both experiments, therefore, undeniably serve as strong affirmations that this technology can one day be applicable and beneficial to humans. However, given that this technology was just recently translated from a proof of principle, more improvements and many more years of development would have to be done in order to create a bioartificial organ with 100% functionality that will be safe and effective for humans.

The current technology of using acellular organ scaffolds and patient-derived cells for organ regeneration is still at its initial stage of development and therefore require funding to fuel advancements and make this technology accessible to everyone. The technology of utilizing Oct3/4, Sox2, c-Myc, and Klf43 to transform human somatic cells into pluripotent stem cells, and from it create all human cell types with self-renewal abilities, makes this this an ever-expanding industry with limitless potential. Specifically, this method of using stem cells to create patient-specific organ transplants will revolutionize the field of regenerative medicine and resolve many existing problems caused by the current method of organ transplantation listed previously, making this company a very promising long-term investment.

Lastly, with the endless applications and possibilities of technology such as personalized multiple organ transplantation, cell therapy, tissue regeneration for injuries and graft transplantation, I truly believe that the technology developed by this company will not only be a feasible alternative for organ transplantation, but will eventually replace the existing solution, which is unfortunately insufficient to cope with the current increasing demands for organs and tissues.

References

1. Fisherman, J.A., Greenwald, M.A., Grossi, P.A. Transmission of infection with human allografts: essential considerations in donor screening. Clinical Infectious Disease 55, 720–727 (2012). https://academic.oup.com/cid/article/55/5/720/352345
2. Kitano, K., Schwartz, D.M., Zhou, H., Gilpin, S.E., Wojtkiewicz, G.R., Ren, X., Sommer, C.A., Capilla, A.V., Mathisen, D.J., Goldstein, A.M., Mostoslavsky, G., Ott, H.C. Bioengineering of functional human induced pluripotent stem cell-derived intestinal grafts. Nature Communications 8, 765 (2017). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5635127
3. Madariaga, M.L.L., Ott, H.C. Bioengineering Kidneys for Transplantation. Semin Nephrol 34, 384–393 (2014). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4373354/
4. Moser, P.T., Ott, H.C. Recellularization of organs: what is the future for solid organ transplantation? Current Opinion in Organ Transplantation 19, 603-609 (2014). https://www.ncbi.nlm.nih.gov/pubmed/25304814
5. Song, J.J., Guyette, J.,Gilpin, S., Gonzalez, G., Vancanti, J.P., Ott, H.C. Regeneration and Experimental Orthotopic Transplantation of a Bioengineered Kidney. Nat Med 19, 646-651 (2013). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3650107/