A Humanized Mouse Model Generated Using Surplus Neonatal Tissue

Stem Cell Reports. 2018 Apr 10;10(4):1175-1183. doi: 10.1016/j.stemcr.2018.02.011. Epub 2018 Mar 22.

Abstract

Here, we describe the NeoThy humanized mouse model created using non-fetal human tissue sources, cryopreserved neonatal thymus and umbilical cord blood hematopoietic stem cells (HSCs). Conventional humanized mouse models are made by engrafting human fetal thymus and HSCs into immunocompromised mice. These mice harbor functional human T cells that have matured in the presence of human self-peptides and human leukocyte antigen molecules. Neonatal thymus tissue is more abundant and developmentally mature and allows for creation of up to ∼50-fold more mice per donor compared with fetal tissue models. The NeoThy has equivalent frequencies of engrafted human immune cells compared with fetal tissue humanized mice and exhibits T cell function in assays of ex vivo cell proliferation, interferon γ secretion, and in vivo graft infiltration. The NeoThy model may provide significant advantages for induced pluripotent stem cell immunogenicity studies, while bypassing the requirement for fetal tissue.

Keywords: NeoThy; PSC; hematopoietic stem cells; humanized mouse; iPSC; immunogenicity; immunology; induced pluripotent stem cells; thymus; transplantation.

Publication types

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

MeSH terms

  • Animals
  • Cell Survival
  • Humans
  • Induced Pluripotent Stem Cells / cytology
  • Induced Pluripotent Stem Cells / transplantation
  • Infant, Newborn
  • Mice
  • Models, Animal
  • Myocytes, Cardiac / cytology
  • Thymus Gland / transplantation*