Looking beyond the human for support

The Future of Transplantation

–Preeyati Chopra , 3rd Year MBBS

Government Medical College, Patiala, Punjab

Organ transplantation is one of the medical miracles of the 20th century and remains in many cases the only effective therapy for end-stage organ failure. (1)

It has been more than 50 years since the first transplantation procedure was done under the directive of Dr. Joseph Murray at Boston. The field of transplantation medicine has achieved a commendable feat by giving life to people who thought they would not survive for more than a few weeks because of their damaged organ.

At present however, this method of treatment faces many unsolved problems from insufficient number of available organs, chronic deterioration of allograft function to necessity of life-long immunosuppressive medication which brings about some serious adverse effects. (2)

Needless to say, the medical field has been looking towards newer techniques to overcome these problems. Extensive research is underway on regenerative medicine, cloning, xenotransplantation and organ preservation, to name a few.

Regenerative medicine is defined as the process of replacing or “regenerating” human cells, tissues or organs to restore normal function. This field works on the principle of regenerating damaged tissues and organs in the body by replacing damaged tissue or by stimulating the body’s own repair mechanisms to heal the damaged tissues or organs, which may involve the use of stem cells. Some examples include cell therapies (the injection of stem cells or progenitor cells); immunomodulation therapy (regeneration by biologically active molecules administered alone or as secretions by infused cells); and tissue engineering (transplantation of laboratory grown organs and tissues). (3)

Regenerative medicine has a lot of scope for advancement when combined with therapeutic cloning (also known as somatic cell nuclear transfer, provides an alternative source of transplantable cells). This technique is used to generate early stage embryos that are then explanted in culture to produce embryonic stem cell lines whose genetic material is identical to that of its source.

Thus, these autologous stem cells have the potential to become almost any type of cell in the adult body and would be useful in tissue and organ replacement applications. The use of transplantable tissue and organs derived from therapeutic cloning may lead to the avoidance of immune responses that typically are associated with transplantation of non-autologous tissues. (4)

As a result, along with bypassing the problem of organ shortage, the variety of serious and potentially life-threatening complications associated with immunosuppressive treatments could also be avoided with the use of regenerative medicine and therapeutic cloning.

Moving on to another wide area of research: Xenotransplantation. It is the transplantation of living cells, tissues or organs from one species to another. Despite the promise of offering unlimited and prompt supply of organs, this technique has also been highly scrutinized as it leads to a fear of lethal zoonoses via the xenotransplants.

Most investigators, through years of research on various non-primates, have agreed that the pig would be the most appropriate xenograft source animal for a number of reasons, including size, availability, breeding characteristics, and physiologic similarities to human beings.

Although cross-species transplantation between pig and humanssolved the problem of the availability of the organs, the complication of a hyper-acute rejection (HAR) of xenotransplants still posed a major threat. This is predominantly the reason why the clinical application of xenotransplantation had been held back. (5)

Most major advances that have been made in this field have resulted from the introduction of genetically-engineered pigs or novel immunosuppressive agents. Progress in gene editing procedures and most recently CRISPR technology have made the production of genetically-engineered pigs easier. (6)

Yet even with these modifications, it is not yet clear that the use of clinically acceptable levels of immunosuppression could permit xenograft survivals similar to those of allografts. 

Judicious combination of modifying host immunity and genetically engineering swine donors are likely to lead to clinical success of xenotransplantation in the near future.(5)

Last but not the least, organ preservation which has been described as ‘the supply line for organ transplantation’.

This is essentially the ability to slow down the biological deterioration of organs when removed from their normal physiological environment. The main goal is to maintain function of the organ and tissue during storage so that the graft will function at re-perfusion.

There are currently two approaches of preservation for most transplantable organs: static or dynamic. Simple static cold storage (SCS) is the main method for static storage, while hypothermic machine perfusion (HMP) and other perfusion-based methods such as normothermic machine perfusion and oxygen persufflation comprise the methods for dynamic preservation. Of these 4 methods, only SCS and HMP are currently approved clinically for kidneys, and only SCS for livers, lungs, pancreas, or heart.(7)

In a logistical sense, ‘preservation’ buys ‘time’ and thus improving the current approaches of organ preservation can prevent the massive problem of faster organ deterioration which in turn can lead to more people getting the organ.

The future of transplantation is one with endless possibilities but turning them into a reality depends on a variety of factors from continual research in the field to improve the safety of these techniques to the eventual affordability of these treatment options by the affected individuals.

“Progress lies not in enhancing what is, but in advancing toward what will be.” – Kahlil Gibran

References

1.        Sayegh MH, Carpenter CB. Transplantation 50 years later – Progress, challenges, and promises. N Engl J Med. 2004;351(26):2761–6.

2.        Rowiński W. Future of transplantation medicine. Ann Transplant. 2007;12(1):5–10.

3.        Advancing Transfusion and Cellular Therapies Worldwide. Cord Blood and Regenerative Medicine [Internet]. 2020. p. 2020. Available from: http://www.aabb.org/aabbcct/therapyfacts/Pages/regenerative.aspx

4.        Koh CJ, Atala A. Therapeutic cloning applications for organ transplantation. Transpl Immunol. 2004;12(3–4):193–201.

5.        Sykes M, Sachs DH. Transplanting organs from pigs to humans. Sci Immunol. 2019;4(41).

6.        et al. C. 乳鼠心肌提取 HHS Public Access. Physiol Behav. 2016;176(1):139–48.

7.        Guibert EE, Petrenko AY, Balaban CL, Somov AY, Rodriguez J V., Fuller BJ. Organ preservation: Current concepts and new strategies for the next decade. Transfus Med Hemotherapy. 2011;38(2):125–42.