The Current Status of Organ Transplantation: Exciting Developments

The idea of organ transplantation has long permeated the medical field. From the ancient myths of Cosmos and Damien to 16th-century references of skin flap transplantations to replace missing noses,^3,13 organ transplantation has been an alluring promise. As such, extensive work has been done in this revolutionary field, which has propelled us into the modern era of transplantation. Now, with the advent of novel immunosuppressive regimens and an increased understanding of the precise mechanisms behind cellular rejection, organ transplantations have had a new wave of success and increasingly play a critical role in treating certain conditions.

History and Basics of Organ Transplantation:

The most common form of organ transplantation conducted in medicine is called allotransplantation and involves the transplanting of tissues between members of the same species.¹ Within this general category, research has focused on two main sub-categories based on the kinds of tissues transplanted.

The first primary type, called solid organ transplants (SOTs), involve the transplant of just one tissue type. SOTs first had widespread clinical research performed on them in the early 1950s when advances in surgical techniques and pharmacological immunosuppression made SOTs far safer. Early success included the first successful kidney transplant between identical twins in 1954 and the first successful liver transplant in 1967.^2,14 Spurred on by these innovations, research was accelerated with more successful transplants and advances in rejection management in the following years. This progress continues today, as SOTs still see success.

The second class of transplants is called vascularized composite tissue allotransplantation (VCA) and involves the transplantation of more than one type of tissue. While the concept of VCAs was not new in the 1950s, these were significantly more complicated than SOT due to the difficulty in managing the differing rejection mechanisms of various tissues. However, the same innovations that proliferated SOTs also worked to grow VCAs with technologies such as combination immunosuppressants, making rejection much more controllable.^5,6 From there, the technique was further refined, such as the first successful larynges-tracheal transplant in 1988 and the first successful hand transplants in 1998. This brings us to modern times, where more than 100 upper extremities and approximately 40 face transplants have been performed worldwide.⁷

Advancements in Immunosuppressive Regimens:

One of the key components of successful organ transplantation has been using immunosuppressive medications to mitigate the risk of rejection. Rejection is the process wherein the host’s immune system attacks and destroys the donor organ because it is recognized as a foreign substance. Despite several advances in immunosuppressive regimens, these medications continue to impose several side effects, such as increased susceptibility to infections and increased risk of osteoporosis.¹² However, novel research shows great promise in improving outcomes over the coming years. For example, a 2021 study worked to understand the relationship between various body composition parameters and the metabolism rates of immunosuppressive medications. Results were promising as the researchers found that by looking at each individual’s particular characteristics, physicians were better able to dose immunosuppressive medications and produce better patient outcomes.⁸ Current research is also working to better understand the rejection process itself and ways that could be used to bypass this effect. For example, another 2021 study investigated the process of desensitization for kidney transplants. This process involves training the host’s immune system to better tolerate the donor’s organs to prevent a strong attack.¹⁶ Results were promising, paving the way for a lesser dependence on immunosuppressive medications in the future.

However, despite significant advances in immunosuppressive regimens making allotransplantation more viable, another grave issue plaguing the industry is the lack of viable organs to transplant into patients. For example, a 2017 study found that in 2016, an estimated 98,000 patients started on the organ donation waiting list, and only around 20% of these individuals were able to receive a transplant, and that only after an indeterminate waiting period. Even more shockingly, the study found that since 2005, over 9000 patients on the organ reception list have died or became too ill for transplant.⁴ To solve this crisis, some researchers are exploring more innovative frontiers in the novel realms of synthetic organ production and xenotransplantation.

Advancements in Synthetic Organs:

While the initial concept of synthetic tissues was posited more than 30 years ago, recent developments in tissue engineering and synthetic biology have propelled this field into newfound possibilities. This process mainly involves culturing various cells on an artificial scaffold that allows for the creation of synthetic tissue. Within this field, one of the significant advances in recent years has been the advent and sophistication of various 3D printing techniques allowing for ever more complex tissue growth.⁹ To date, supplemental bladders, small arteries, skin grafts, cartilage and an entire trachea have been experimentally implanted in patients.^11,15 However, propelled by these successes, scientists continue to experiment with even more tissues, including nerve, liver, bone, heart valves and kidneys.

Advancements in Xenotransplantation:

Another area of interest for researchers to combat the lack of organs has been xenotransplantation. Xenotransplantation is defined as any procedure that involves the transferring of cells or fluids between members of different species.¹⁰ While research in this field has been going on since the 1960s, modern innovations in genetic engineering and immunology have brought newfound interest. For example, after identifying the key markers driving rejection between pigs and humans, scientists have now used cutting-edge techniques, such as CRISPR/Cas9, to breed knockout pigs theoretically compatible with the human immune system. In an experiment in the baboon model, non-life-sustaining pig hearts remained viable for almost 945 days.¹⁰ Different techniques in infection management have also lowered the risk of zoonotic illness transmission, paving a bright path forward for xenotransplantation to gain wider medical use.

Thus, organ transplants have had a fascinating history and continue to be an area of significant research. Combining innovations in various biological fields, this area is a shining model for the importance of interdisciplinary science. Hopefully, steady progress continues so that organ transplantation can fulfill its initial promise to revolutionize medicine.

References

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