6. Organ & tissue preservation as a transformative platform technology

Abstract

The ability to preserve organs and tissues outside of the body for periods exceeding even a few hours is a longstanding medical goal that if achieved could eliminate death resulting from solid organ failure and disability from trauma, burns, and amputation. In the last 50 years only incremental progress has been made in this area, largely due to public and private underinvestment and a fragmented scientific effort with few interdisciplinary synergies or collaborative efforts. However, there is growing evidence of rapid technological convergence that hints at a revolution in this field. Previously inaccessible approaches to slow down or stop biological time are now being enabled by this rapid convergence. Concrete examples of this can be found in the enabling work of fields not normally associated with cryobiology. High performance computing, thermo-mechanical modeling of biological systems, high-throughput cryo-protectant screening, and micro-physiological platforms (organ-on-a-chip systems), are all starting play a role in answering key questions about how to protect biological systems in sub-normo-thermic regimes, and indeed even at the sub-zero temperatures that would permit longer preservation on the order of days to years. A true organ and tissue banking capability would transform medicine as we know it. Even if this were as modest as extending the time that an organ or tissue could be preserved to 48 h instead of the current 2–8 h as it is for some solid organs, it would enable a whole host of curative therapies that are currently off limits. One can envision the impact this would have: organ waiting lists could disappear; HLA matching/could be ideal the majority of the time instead of just a fraction of the time, thus doubling 5-year survival rates; survival rates for non-metastatic cancers of a vital organ (such as liver or lung) would immediately spike to above 90% due to routine organ replacement; the entire field of tissue engineering would be able to give their products a shelf-life thus unleashing the true potential of engineered tissues and creating new markets. The impact would be immediate and transformational. Induction of immune tolerance for allogeneic tissues is an emerging area of transplant medicine that seeks to overcome immune rejection. Tolerance induction is a factor in all donated tissues and will become an important consideration for any engineered tissues. The key factor for inducing immune tolerance is time. Whether through hematopoietic chimerism, or intrathymic transplant, the body requires 2–3 weeks to adapt to the allogeneic environment, during which time the donor organ must be preserved in waiting until tolerance is fully induced and the transplant can proceed. In cases of trauma, the ability to preserve tissue and severed limbs until advanced surgery is possible would mean far fewer amputations and vastly superior outcomes following reconstruction. This has tremendous implications for military trauma treatment. In practice many traumatic injuries that result in limb severance could be corrected surgically with good outcomes; however, the expertise to perform these procedures is usually more than 48 h away from the point of injury on the battlefield. The DoD’s Tissue Injury and Regenerative Medicine Program Office which oversees the Armed Forces Institute of Regenerative Medicine (AFIRM) also oversees the DoD’s arm and face transplant programs. Together these constitute close to $1B in federal investment. The entirety of this portfolio would benefit from the emergence of an organ and tissue banking capability.