Neonatal immune-tolerance in mice does not prevent xenograft rejection

Exp Neurol. 2014 Apr:254:90-8. doi: 10.1016/j.expneurol.2014.01.007. Epub 2014 Jan 16.

Abstract

Assessing the efficacy of human stem cell transplantation in rodent models is complicated by the significant immune rejection that occurs. Two recent reports have shown conflicting results using neonatal tolerance to xenografts in rats. Here we extend this approach to mice and assess whether neonatal tolerance can prevent the rapid rejection of xenografts. In three strains of neonatal immune-intact mice, using two different brain transplant regimes and three independent stem cell types, we conclusively show that there is rapid rejection of the implanted cells. We also address specific challenges associated with the generation of humanized mouse models of disease.

Keywords: Huntington's disease; Immune rejection; Neonatal immunity; Neonatal tolerance; Xenograft.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Animals, Outbred Strains
  • Cells, Cultured
  • Corpus Striatum / cytology
  • Disease Models, Animal
  • Female
  • Graft Rejection / immunology*
  • Graft Rejection / prevention & control
  • Graft Survival / immunology
  • Heterografts / immunology*
  • Humans
  • Huntingtin Protein
  • Huntington Disease / genetics
  • Huntington Disease / immunology
  • Huntington Disease / therapy*
  • Immune Tolerance / immunology*
  • Male
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Mice, Transgenic
  • Nerve Tissue Proteins / genetics
  • Neural Stem Cells / immunology*
  • Neural Stem Cells / transplantation*
  • Nuclear Proteins / genetics
  • Transplantation, Heterologous

Substances

  • Htt protein, mouse
  • Huntingtin Protein
  • Nerve Tissue Proteins
  • Nuclear Proteins