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2015 ; 22
(2
): 95-101
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Review on porcine endogenous retrovirus detection assays--impact on quality and
safety of xenotransplants
#MMPMID25641488
Godehardt AW
; Rodrigues Costa M
; Tönjes RR
Xenotransplantation
2015[Mar]; 22
(2
): 95-101
PMID25641488
show ga
Xenotransplantation of porcine organs, tissues, and cells inherits a risk for
xenozoonotic infections. Viable tissues and cells intended for transplantation
have to be considered as potentially contaminated non-sterile products. The
demands on microbial testing, based on the regulatory requirements, are often
challenging due to a restricted shelf life or the complexity of the product
itself. In Europe, the regulatory framework for xenogeneic cell therapy is based
on the advanced therapy medicinal products (ATMP) regulation (2007), the EMA CHMP
Guideline on xenogeneic cell-based medicinal products (2009), as well as the WHO
and Council of Europe recommendations. In the USA, FDA guidance for industry
(2003) regulates the use of xenotransplants. To comply with the regulations,
validated test methods need to be established that reveal the microbial status of
a transplant within its given shelf life, complemented by strictly defined action
alert limits and supported by breeding in specific pathogen-free (SPF)
facilities. In this review, we focus on assays for the detection of the porcine
endogenous retroviruses PERV-A/-B/-C, which exhibit highly polymorphic proviral
loci in pig genomes. PERVs are transmitted vertically and cannot be completely
eliminated by breeding or gene knock out technology. PERVs entail a public health
concern that will persist even if no evidence of PERV infection of xenotransplant
recipients in vivo has been revealed yet. Nevertheless, infectious risks must be
minimized by full assessment of pigs as donors by combining different molecular
screening assays for sensitive and specific detection as well as a functional
analysis of the infectivity of PERV including an adequate monitoring of
recipients.