Publications by authors named "Barbara Gulich"

Porcine cytomegalovirus (PCMV) is widely distributed in pigs and difficult to detect due to latency. PCMV infection of source pigs was associated with early graft failure after cardiac and renal xenotransplantation into nonhuman primates. Importantly, PCMV infection of the first genetically modified pig heart into a human may have contributed to the reduced survival of the patient.

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Article Synopsis
  • Xenotransplantation uses pigs as organ donors to address the shortage of human transplantable organs, but there are concerns about infectious retroviruses in pigs.
  • Research identified a full-length porcine endogenous retrovirus (PERV-C) in SLA haplotype pigs, which have a lower risk of carrying harmful retroviruses.
  • The study mapped the virus's chromosome location and demonstrated its increased infectivity, contributing to efforts aimed at creating PERV-C-free pigs for safer organ transplantation.
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Introduction: Porcine endogenous retroviruses (PERVs) are an integral part of the pig genome with infectious potential, as shown in vitro.

Hypothesis/gap Statement: In view of nonclinical and clinical xenotransplantation, data are essential that give an insight into viral pathogenicity. This includes PERV's environmental stability and environmental risk.

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Background: Decellularized human pulmonary heart valve (dhHV) scaffolds have been shown to be the gold standard especially for younger, adolescent patients. However, human heart valves are limited in availability. Xenogeneic decellularized pig heart valves (dpHV) may serve as alternative.

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The infection of human transplant recipients by porcine endogenous retrovirus (PERV) is a safety issue for xenotransplantation (XTx). CRISPR/Cas9 technology has enabled the generation of pigs free of functional PERVs, and the susceptibility of these animals to reinfection by PERVs remains unclear. To assess virological safety, we characterized a cell line in which PERVs have been inactivated by CRISPR/Cas9 (PK15 clone 15) for its susceptibility to infectious PERV.

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Background: Porcine induced pluripotent stem cells (piPSCs) offer an alternative strategy in xenotransplantation (XTx). As human endogenous retroviruses (HERV), particularly HERV-K, are highly expressed in natural human stem cells, we compared the expression of porcine endogenous retroviruses (PERV) and retrotransposon LINE-1 (L1) open reading frames 1 and 2 (pORF1 and pORF2) in different piPSC-like cell lines with their progenitors (porcine fetal fibroblasts, pFF).

Methods: Cells reprogrammed via Sleeping Beauty-transposed transcription factors were cultured and analyzed on a custom-designed microarray representing the reference pig genome.

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Background: Porcine endogenous retroviruses (PERV) pose a zoonotic risk potential in pig-to-human xenotransplantation given that PERV capacity to infect different human cell lines in vitro has been clearly shown in the past. However, PERV infectious potential for human peripheral blood mononuclear cells (huPBMC) has been also demonstrated, albeit with controversial results. As productive PERV infection of huPBMC involves immune suppression that may attract opportunistic pathogens as shown for other retroviruses, it is crucial to ascertain unequivocally huPBMC susceptibility for PERV.

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