The need for xenotransplantation as a source of organs and cells for clinical transplantation

Abstract

The limited availability of deceased human organs and cells for the purposes of clinical transplantation remains critical worldwide. Despite the increasing utilization of 'high-risk', 'marginal', or 'extended criteria' deceased donors, in the U.S. each day 30 patients either die or are removed from the waiting list because they become too sick to undergo organ transplantation. In certain other countries, where there is cultural resistance to deceased donation, e.g., Japan, the increased utilization of living donors, e.g., of a single kidney or partial liver, only very partially addresses the organ shortage. For transplants of tissues and cells, e.g., pancreatic islet transplantation for patients with diabetes, and corneal transplantation for patients with corneal blindness (whose numbers worldwide are potentially in the millions), allotransplantation will never prove a sufficient source. There is an urgent need for an alternative source of organs and cells. The pig could prove to be a satisfactory source, and clinical xenotransplantation using pig organs or cells, particularly with the advantages provided by genetic engineering to provide resistance to the human immune response, may resolve the organ shortage. The physiologic compatibilities and incompatibilities of the pig and the human are briefly reviewed.

Keywords: Cell transplantation; Organ shortage; Organ transplantation; Pig; Xenotransplantation.

Figure 1. Trends in the numbers of organ donors (blue), organ transplants (red), and patients on the waiting list (black) in the U.S., 1991–2013

In 1991, there were 6,953 donors, 15,757 organ transplants, and 23,198 patients on the waiting list. By 2013, there were 14,257 donors, 28,954 organ transplants, and 121,272 patients on the waiting list. (Data obtained from http://optn.transplant.hrsa.gov.)

Figure 2. Longest reported survival times of pig organ and cell xenotransplantation in preclinical trials (pig-to-nonhuman primate models)

Microencapsulated pancreatic islets = 804 days (with re-Tx), 250 days (without re-Tx) (Sun et al [35]) (wild-type [WT] pigs); Neuronal cells = >521 days (Badin et al [31]) (CTLA4-Ig transgenic pigs); pancreatic islets = 396 days (van der Windt et al [36]) (hCD46 pigs); cornea (full thickness) = >933 days (Choi et al [37]) (WT pigs); hepatocytes = 243 days (with re-Tx), 80 days (without re-Tx) (Nagata et al [38]) (WT pigs); heterotopic heart = >500 days (Mohiuddin et al [18]) (GTKO/hCD46/hTBM pigs); kidney = >240 days (Tector AJ, personal communication) (GTKO/hCD55 pigs); orthotopic heart = 57 days (McGregor et al [19]) (GTKO/hCD55 pigs); liver = 9 days (Kim K et al [28]) (hCD55 pigs); lung = 5 days (Cantu et al [29]) (vWF-deficient pigs). Figure modified from Ekser B et al. [15].