Low Immunogenicity and Immunosuppressive Properties of Human ESC- and iPSC-Derived Retinas

Stem Cell Reports. 2021 Apr 13;16(4):851-867. doi: 10.1016/j.stemcr.2021.02.021. Epub 2021 Mar 25.

Abstract

ESC- and iPSC-derived retinal transplantation is a promising therapeutic approach for disease with end-stage retinal degeneration, such as retinitis pigmentosa and age-related macular degeneration. We previously showed medium- to long-term survival, maturation, and light response of transplanted human ESC- and iPSC-retina in mouse, rat, and monkey models of end-stage retinal degeneration. Because the use of patient hiPSC-derived retina with a disease-causing gene mutation is not appropriate for therapeutic use, allogeneic transplantation using retinal tissue/cells differentiated from a stocked hESC and iPSC line would be most practical. Here, we characterize the immunological properties of hESC- and iPSC-retina and present their three major advantages: (1) hESC- and iPSC-retina expressed low levels of human leukocyte antigen (HLA) class I and little HLA class II in vitro, (2) hESC- and iPSC-retina greatly suppressed immune activation of lymphocytes in co-culture, and (3) hESC- and iPSC-retina suppressed activated immune cells partially via transforming growth factor β signaling. These results support the use of allogeneic hESC- and iPSC-retina in future clinical application.

Keywords: ESCs; iPSCs; inflammation; retina; suppression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation* / drug effects
  • Histocompatibility Antigens Class I / metabolism
  • Human Embryonic Stem Cells / cytology*
  • Human Embryonic Stem Cells / drug effects
  • Human Embryonic Stem Cells / transplantation
  • Humans
  • Immunomodulation / drug effects
  • Immunosuppression Therapy*
  • Induced Pluripotent Stem Cells / cytology*
  • Induced Pluripotent Stem Cells / drug effects
  • Induced Pluripotent Stem Cells / metabolism
  • Interferon-gamma / pharmacology
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / metabolism
  • Primates
  • Recombinant Proteins / pharmacology
  • Retina / immunology*
  • Retinal Pigment Epithelium / cytology
  • Transforming Growth Factor beta / metabolism

Substances

  • Histocompatibility Antigens Class I
  • Recombinant Proteins
  • Transforming Growth Factor beta
  • Interferon-gamma