Immune parameters relevant to neural xenograft survival in the primate brain

Francesca Cicchetti, W. Fodor, T. W. Deacon, C. Van Horne, S. Rollins, W. Burton, L. C. Costantini, O. Isacson

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

The lack of supply and access to human tissue has prompted the development of xenotransplantation as a potential clinical modality for neural cell transplantation. The goal of the present study was to achieve a better understanding of the immune factors involved in neural xenograft rejection in primates. Initially, we quantified complement mediated cell lysis of porcine fetal neurons by primate serum and demonstrated that anti-C5 antibody treatment inhibited cell death. We then developed an immunosuppression protocol that included in vivo anti-C5 monoclonal antibody treatment, triple drug therapy (cyclosporine, methylprednisolone, azathioprine) and donor tissue derived from CD59 or H-transferase transgenic pigs and applied it to pig-to-primate neural cell transplant models. Pre-formed αGal, induced αGal and primate anti-mouse antibody (PAMA) titers were monitored to assess the immune response. Four primates were transplanted. The three CD59 neural cell recipients showed an induced anti-αGal response, whereas the H-transferase neural cell recipient exhibited consistently low anti-αGal titers. Two of these recipients contained surviving grafts as detected by immunohistochemistry using selected neural markers. Graft survival correlated with high dose cyclosporine treatment, complete complement blockade and the absence of an induced PAMA response to the murine anti-C5 monoclonal antibodies.

Original languageEnglish
Pages (from-to)41-49
Number of pages9
JournalXenotransplantation
Volume10
Issue number1
DOIs
StatePublished - Jan 2003

Keywords

  • Dopamine
  • Immune response
  • Neurodegenerative disorder
  • Striatum
  • Xenotransplantation

ASJC Scopus subject areas

  • Immunology
  • Transplantation

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