Bioengineering approaches to organ preservation ex vivo

Abstract

The advent of successful solid organ transplantation is undoubtedly among the most significant medical achievements of the 20th century. Despite advances in the field of transplantation since its inception over 50 years ago, our approach to donor organ preservation outside of the body remains unchanged. Recently, attempts have been made to replace static cold storage with more sophisticated ex vivo machine perfusion. Rather than cooling the organ on ice to slow metabolic processes, machine perfusion aims to support normal metabolic function in a near-physiologic environment and to provide a platform on which the organ can be evaluated, preserved, and recovered. Ex vivo machine perfusion devices have demonstrated early success with respect to transplant outcomes in heart, lung, and liver, with perfusion times limited to several hours. The continued development of more advanced perfusion systems is likely to extend the duration of ex vivo organ support to days or even weeks, and enable recovery of initially unsuitable donor organs. In this review, we discuss recent clinical and pre-clinical studies, state-of-the-art organ preservation technologies, existing limitations, and a perspective on future developments.

The Cellular and Physiological Basis for Lung Repair and Regeneration: Past, Present, and Future

“…Notably, many of the conditions that render donor lungs unacceptable for transplantation (e.g., aspiration, infection, pulmonary contusions) could be reversible. However, conventional methods of donor lung preservation that involve cold static ischemia preclude endogenous repair and recovery (Guibert et al, 2011;Pinezich and Vunjak-Novakovic, 2019). The field of ex vivo lung perfusion (EVLP) is now addressing this limitation by providing initially unacceptable donor lungs with physiologic conditions of normothermia, perfusion, and ventilation, to recover function outside the body to a level acceptable for transplantation (Makdisi et al, 2017;Tane et al, 2017).…”

Multiday maintenance of extracorporeal lungs using cross-circulation with conscious swine

“…Lungs recovered by XC would then be transplanted into the patient, thereby potentially decreasing the morbidity and mortality associated with transplantation of injured lungs. Future investigations using multiday extracorporeal organ support could also enable advanced interventions through immunomodulation, 28,29 cell replacement, 17,[30][31][32][33] or other bioengineering approaches, 17,32,[34][35][36] and ultimately serve as a platform to improve transplant outcomes.…”

“…2,3 Many of the conditions that render donor lungs unacceptable for transplantation (eg, aspiration, infection, and pulmonary contusions) are potentially reversible, but conventional methods of donor lung preservation rely on nonphysiologic cold static ischemia and preclude endogenous repair and recovery. 4,5 Ex vivo lung perfusion (EVLP) aims to address these limitations by providing initially unacceptable donor lungs with physiologic conditions-normothermia, perfusion, ventilation-to recover function outside the body to a level acceptable for transplantation. 6,7 Since the introduction of EVLP by Steen and colleagues in 2001, 8 EVLP platforms have demonstrated short-term support and recovery of marginal quality donor lungs in preclinical and clinical settings.…”

Bioengineering of Pulmonary Epithelium With Preservation of the Vascular Niche

“…Development of pulmonary edema, diminished gas exchange capability, and deterioration of the endothelial-epithelial barrier remain ubiquitous and formidable challenges that hinder the effectiveness of EVLP in providing long-term support. To address these limitations, our group recently introduced a novel XC platform for extracorporeal lung support using a large animal model (swine) Guenthart et al, 2019b;Pinezich and Vunjak-Novakovic, 2019). In XC setting, the lung being recovered is placed into an EVLP-like organ chamber, ventilated in a normothermic, humidified environment, and connected to the blood perfusion with a swine recipient (Figure 3A) .…”