The promise of organ and tissue preservation to transform medicine

Abstract

The ability to replace organs and tissues on demand could save or improve millions of lives each year globally and create public health benefits on par with curing cancer. Unmet needs for organ and tissue preservation place enormous logistical limitations on transplantation, regenerative medicine, drug discovery, and a variety of rapidly advancing areas spanning biomedicine. A growing coalition of researchers, clinicians, advocacy organizations, academic institutions, and other stakeholders has assembled to address the unmet need for preservation advances, outlining remaining challenges and identifying areas of underinvestment and untapped opportunities. Meanwhile, recent discoveries provide proofs of principle for breakthroughs in a family of research areas surrounding biopreservation. These developments indicate that a new paradigm, integrating multiple existing preservation approaches and new technologies that have flourished in the past 10 years, could transform preservation research. Capitalizing on these opportunities will require engagement across many research areas and stakeholder groups. A coordinated effort is needed to expedite preservation advances that can transform several areas of medicine and medical science.

Figure 1

The true lifesaving potential of organ transplantation. The roughly 50,000 US patients added to transplant waiting lists in 2011 were outnumbered over 14-fold by those who died from end-stage organ disease (http://www.perfusix.com/impact-of-ex-vivo.html), without counting cases where malignancies could have been treated with organ replacement. This suggests that the true size of the organ shortage could be many times larger than is reflected by transplant waiting lists (currently 120,000 US patients).

Figure 2

The global unmet need for transplantation greatly exceeds that of the United States (see Fig. 1), which contains roughly 4% of the world’s population but performs 25% of its organ transplants. By comparison, the continent of Africa contains roughly 16% of the world’s population but performs fewer than 0.5% of its organ transplants (http://www.transplant-observatory.org/summary/; https://esa.un.org/unpd/wpp/publications/files/key_findings_wpp_2015.pdf).

Figure 3

10-year graft survival for each of the six vital organs currently transplanted (single-organ, deceased donor transplant). 10-year survival rates for organs range from slightly over 50% (hearts and livers) to slightly over 25% (lungs and intestine). These data indicate that ensuring transplant organ quality and reducing susceptibility to chronic rejection are still major challenges in transplantation. Preservation advances present diverse opportunities to meet these challenges (Table 2).

Figure 4

An integrated approach to organ and tissue preservation would combine multiple preservation conditions and temperature ranges, drawing on the strategies found in Table 4. Thus, when called for, differing preservation modalities could be used during successive stages of the preservation process, accessing a much wider range of temperatures and conditions than are currently used in conventional organ preservation. For instance, transplant organs could be held at subnormothermic temperatures during pharmacological pre-conditioning for cryopreservation, then cooled to cryogenic temperatures for transport or banking, then returned to near-normothermic temperatures for functional assessment. Many combinations are conceivable based on the diverse proof-of-principle discoveries; the optimal preservation protocol will most likely vary according to tissue type and application.