Limiting potential infectious risks of transplanting insulin-producing pig cells into humans

Aims: Prior to commencing a study of grafting foetal/neonatal pig islet-like cell clusters into type I diabetic human subjects, the microbiological risks of transplanting porcine pancreatic tissue were assessed. Methods: An exclusion list for screening donor animals and graft tissue in Australia was compiled following evaluation of the disease risks posed by 121 organisms, including 36 bacteria, 12 fungi, four mycoplasma, 31 parasites and 38 viruses. The list of evaluated agents was derived from the literature, interviews with veterinarians and physicians, and a survey of laboratories. Results: The exclusion list contains 35 organisms (including 20 bacteria, four fungi, one mycoplasma, one parasite and nine viruses) that are zoonotic, pathogens of immunocompromised hosts (including human allograft recipients), pathogens resistant to antibiotics or potentially able to recombine with the human genome. These 35 agents can be detected by culture (e.g., Actinomyces), serological testing (e.g., influenza viruses) or nucleic acid amplification (e.g., Mycobacteria). Conclusions: It is recommended that: (i) source pigs designated for use in human xenotransplantation trials should be tested regularly for the 35 organisms; (ii) the mothers of donor foetal/neonatal pigs and, when possible, the foetal/neonatal pigs themselves should be tested immediately prior to the grafting of tissue into humans; and (iii) the exclusion list be modified for designated source pig herds in countries other than Australia.