Content area
Full text
Received Jul 6, 2017; Accepted Oct 8, 2017
This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
1. Introduction
About 5.7 million Americans have heart failure, half of whom will die within 5 years [1]. Organ transplantation is currently the preferred solution for treatment of end-stage heart failure but less than 3000 heart transplants have been performed annually in the US in recent years. Circulatory assist devices and total artificial hearts have been approved to support patients in chronic heart failure [2, 3]. These mechanical solutions are effective, at least in the short term, but have significant morbidity from thromboembolism, infection, gastrointestinal bleeding, and reduced quality of life [4]. Regenerative solutions for heart failure remain a nascent experimental technology. Cardiac xenotransplantation (CXTx) is a promising viable near-term solution to the shortage of hearts for clinical transplantation. In recent years, there has been a remarkable improvement in survival of heterotopic pig-to-nonhuman primate (NHP) CXTx [5–8], encouraging early success in orthotopic CXTx (oCXTx) [9–11] and advances in life-supporting renal xenotransplantation (RXTx) [12, 13]. These results validate the physiological compatibility of porcine organs, at least in NHPs, and suggest that clinical CXTx may soon be applicable if oCXTx can attain similar improvements in survival as RXTx. In this review, we examine developments in immune suppression, porcine donor genetics, preclinical transplants, and infectious disease issues and discuss requirements for clinical CXTx.
To justify a clinical xenotransplantation (XTx) program, it is necessary to demonstrate transplant efficacy in clinically relevant animal models. The International Society of Heart Lung Transplantation (ISHLT) has suggested that a prospectively defined series of life-supporting cardiac xenotransplants in NHPs, using predefined immune suppression, with “60% survival at 3 months with a minimum of 10 animals surviving for this period,” would be sufficient to consider a clinical trial [14]. The recent survival achieved after heterotopic CXTx (hCXTx), in excess of 2 years and with a median survival of 298 days...