Examining the potential for porcine‐derived islet cells to harbour viral pathogens

Abstract

With an onus on safety in the potential use of porcine islet cells as a treatment for diabetes, the use of animals lacking exogenous pathogens is clearly important and multilevel screening strategies have been presented on testing animals and the product. In this study, we wished to investigate whether islet cells indeed harboured the same viral pathogens of concern in the source animal. PMBC and islet cells from both adult and neonatal source animals were directly compared and tested for PCMV, PLHV, PCV2, PPV and HEV using both molecular and serological assays. Adult PBMC were found positive for all viruses with the exception of PCV2 and HEV. Neonatal PBMC were only found positive for PCMV and HEV. All animals were found negative for HEV antibodies. Interestingly, islet cells were negative for all viruses tested regardless of status in the animal-derived PBMC. Given that other laboratories have demonstrated the lack of virus detection during the culture of islets, this study also demonstrates that the hygiene status of the herd may not reflect the status of the product. This is important for establishing guidelines for any risk evaluation and mitigation process utilised during product manufacture.

Assessment of porcine endogenous retrovirus transmission across an alginate barrier used for the encapsulation of porcine islets

“…Indeed, it has also been suggested that islets may not harbour many of the viral pathogens identified in the donor pig. 17 However, we recognize that this study was conducted for a relatively short time period of 8 weeks and that a longer study would be valuable in examining this further. Although, it should be noted that PK15 cells used in this study are high PERV producers and it is likely a lower barrier of protection is required to protect as against PERV transmission from islet cells.…”

Possible risks posed by single‐stranded DNA viruses of pigs associated with xenotransplantation

“…In general, ssDNA viruses infecting humans and pigs are widely prevalent and have high mutation rates. However, this high prevalence may not hinder the use of pig xenografts, as a recent report highlights that islet cells of pigs do not carry common pig viruses including PCV2 and PPV1, even if other cells such as PBMCs carry them . Indeed, xenotransplantation of islet cells from pigs to cynomolgus monkeys in preclinical trials and from pigs to human patients in clinical trials has been achieved without transmission of any pig viruses including ssDNA viruses such as PPV, PCV1, and PCV2 .…”

The 2017 IXA Presidential Lecture: Recent developments in xenotransplantation

“…Careful husbandry and rigorous screening are critical to exclude pathogenic microorganisms from the donor pig herd . Interestingly, in the case of islets, the product may be “clean” even if the herd is “dirty.” Crossan et al isolated islets from pigs which had tested positive for one or more of five potentially zoonotic viruses in serum or peripheral blood mononuclear cells. All of the islet preparations were found to be negative for all viruses tested.…”