Survival of intrastriatal xenografts of ventral mesencephalic dopamine neurons from MHC-deficient mice to adult rats

Wei Ming Duan, Marcus Westerman, Tina Flores, Walter C Low

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

Previous studies of neural xenografts have used immunosuppressive agents to prevent graft rejection. In the present study we have examined the survival of mouse dopamine neurons lacking either MHC class I or MHC class II molecules transplanted into rat brains and the host immune and inflammatory responses against the xenografts. Survival of neural grafts was immunocytochemically determined at 4 days, 2 weeks, and 6 weeks after transplantation by counting tyrosine hydroxylase (TH)-positive cells in the graft areas. In addition, the host immune and inflammatory responses against neural xenografts were evaluated by semiquantitatively rating MHC class I and class II antigen expression, accumulation of macrophages and activated microglia, and infiltration of CD4- and CD8-positive T-lymphocytes. For the negative controls, the mean number of TH-positive cells in rats that received wild-type mouse tissue progressively decreased at various time periods following transplantation. In contrast, intrastriatal grafting of either MHC class I or MHC class II antigen-depleted neural xenografts resulted in a prolonged survival and were comparable to cyclosporin A-treated rats that had received wild-type mouse tissue. These results indicate that genetically modified donor tissue lacking MHC molecules can be used to prevent neural xenograft rejection.

Original languageEnglish (US)
Pages (from-to)108-117
Number of pages10
JournalExperimental Neurology
Volume167
Issue number1
DOIs
StatePublished - 2001

Keywords

  • Dopamine
  • Immunology
  • Inflammation
  • Major histocompatibility complex antigens
  • Neural transplantation
  • Parkinson's disease
  • Rat

Fingerprint Dive into the research topics of 'Survival of intrastriatal xenografts of ventral mesencephalic dopamine neurons from MHC-deficient mice to adult rats'. Together they form a unique fingerprint.

Cite this