No Evidence for Infection of Human Cells With Porcine Endogenous Retrovirus (Perv) After Exposure to Porcine Fetal Neuronal Cells1

Dinsmore, Jonathan; Manhart, Carolyn J.; Raineri, R.; Moore, Alan

doi:10.1097/00007890-200011150-00020

Cited by 100 publications

(62 citation statements)

References 33 publications

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“…3), suggesting that PERV-A should have the ability to infect many tissue compartments. Functional receptor expression in PBMCs as well as their susceptibility to PERV infection supports the relevance of conclusions drawn from clinical studies that there was no evidence of PERV transmission in the PBMCs of patients exposed to pig tissues or cells (18)(19)(20)22). However, in vitro studies have shown that few human and nonhuman primate cells are permissive for productive infection by PERV-A even if they are susceptible to PERV-A pseudotype entry (3,5,30,33).…”

Section: Discussionsupporting

confidence: 58%

See 1 more Smart Citation

Identification of receptors for pig endogenous retrovirus

Ericsson¹,

Takeuchi

Templin³

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

134

157

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Section: Discussionsupporting

confidence: 58%

“…PBMCs are the most accessible tissue and have been tested for the presence of PERV in patients exposed to live porcine tissues (18)(19)(20)(21)(22). However, sensitivity of PBMCs to PERV entry or infection has not been demonstrated unequivocally (3,23).…”

Section: Perv-a Receptor Expression In Vivomentioning

confidence: 99%

Identification of receptors for pig endogenous retrovirus

Ericsson¹,

Takeuchi

Templin³

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

134

157

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show abstract

“…75 In the human neural xenograft recipients there have been no complications in terms of host infections, nor any demonstration of anti-PERV antibodies, and negative PCRs for PERV. 76 Thus, it would appear that although there are theoretical risks of PERV infection in patients grafted with porcine neural tissue, this is yet to be seen as a major issue in any studies using this tissue.…”

Section: Xenograft and Zoonosesmentioning

confidence: 99%

Immune problems in central nervous system cell therapy

Barker¹,

Widner

2004

Neurotherapeutics

165

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Summary:Transplantation of cells and tissues to the mammalian brain and CNS has revived the interest in the immunological status of brain and its response to grafted tissue. The previously held view that the brain was an absolute "immunologically privileged site" allowing indefinite survival without rejection of grafts of cells has proven to be wrong. Thus, the brain should be regarded as a site where immune responses can occur, albeit in a modified form, and under certain circumstances these are as vigorous as those seen in other peripheral sites. Clinical cell transplant trials have now been performed in Parkinson's disease, Huntington's disease, demyelinating diseases, retinal disorders, stroke, epilepsy, and even deafness, and normally are designed as cell replacement strategies, although implantation of genetically modified cells for supplementation of growth factors has also been tried. In addition, some disorders of the CNS for which cell therapies are being considered have an immunological basis, such as multiple sclerosis, which further complicates the situation. Embryonic neural tissue allografted into the CNS of animals and patients with neurodegenerative conditions survives, makes and receives synapses, and ameliorates behavioral deficits. The use of aborted human tissue is logistically and ethically complicated, which has lead to the search for alternative sources of cells, including xenogeneic tissue, genetically modified cells, and stem cells, all of which can and will induce some level of immune reaction. We review some of the immunological factors involved in transplantation of cells to CNS.

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“…Three of the 12 patients in the first study improved significantly and there were no adverse events related to the use of porcine tissue in these patients [10]. No transmission of porcine endogenous retrovirus (PERV) was detected in any of the transplanted patients [11]. Post-mortem analysis of the brain of one deceased patient that died from a pulmonary embolism 7 months after transplantation, revealed 638 surviving transplanted dopamine cells [12].…”

Section: Introductionmentioning

confidence: 96%

Simultaneous inhibition of B7 and LFA‐1 signaling prevents rejection of discordant neural xenografts in mice lacking CD40L

Larsson

Corbascio

Widner

et al. 2002

Xenotransplantation

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: Transplantation of embryonic human neural tissue can restore dopamine neurotransmission and improve neurological function in patients with Parkinson's disease. Logistical and ethical factors limit the availability of human embryonic allogeneic tissue. Embryonic xenogeneic neural tissue from porcine donors is an alternative form of donor tissue, but effective immunomodulatory techniques are warranted for neural xenotransplantation to become clinically feasible. We transplanted embryonic porcine ventral mesencephalic tissue into the brains of adult untreated C57BL/6 mice, untreated CD40L‐/–mice and CD40L‐/–mice that received injections of anti‐LFA‐1, CTLA4Ig or both compounds. Double‐treated CD40L‐/–mice had large grafts with high numbers of dopaminergic neurons 4 wk after transplantation. The grafts were completely devoid of lymphocytes, macrophages and activated microglia. Untreated C57BL/6 mice had rejected their grafts. Untreated CD40L‐/–mice and CD40L‐/–mice treated with monotherapy of anti‐LFA‐1 or CTLA4Ig had smaller grafts and more microglial and lymphocytic infiltration than double‐treated CD40L‐/–mice. We conclude that immunomodulation with concomitant inhibition of LFA‐1 and B7 signaling in the perioperative period in CD40L‐/–mice prevented the rejection of discordant neural xenografts. The treatment most likely reduced antigen presenting capacity and interfered with the costimulatory signaling needed for T cell activation to occur.

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No Evidence for Infection of Human Cells With Porcine Endogenous Retrovirus (Perv) After Exposure to Porcine Fetal Neuronal Cells1

Abstract: Our results demonstrate by both examination of transplant patient blood samples and in vitro studies that there is no evidence for transmission of PERV from porcine fetal neural cells to human cells.

Cited by 100 publications

References 33 publications

Identification of receptors for pig endogenous retrovirus

Identification of receptors for pig endogenous retrovirus

Immune problems in central nervous system cell therapy

Simultaneous inhibition of B7 and LFA‐1 signaling prevents rejection of discordant neural xenografts in mice lacking CD40L

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