Teratocarcinomas Arising from Allogeneic Induced Pluripotent Stem Cell-Derived Cardiac Tissue Constructs Provoked Host Immune Rejection in Mice

Sci Rep. 2016 Jan 14:6:19464. doi: 10.1038/srep19464.

Abstract

Transplantation of induced pluripotent stem cell-derived cardiac tissue constructs is a promising regenerative treatment for cardiac failure: however, its tumourigenic potential is concerning. We hypothesised that the tumourigenic potential may be eliminated by the host immune response after allogeneic cell transplantation. Scaffold-free iPSC-derived cardaic tissue sheets of C57BL/6 mouse origin were transplanted into the cardiac surface of syngeneic C57BL/6 mice and allogeneic BALB/c mice with or without tacrolimus injection. Syngeneic mice and tacrolimus-injected immunosuppressed allogeneic mice formed teratocarcinomas with identical phenotypes, characteristic, and time courses, as assessed by imaging tools including (18)F-fluorodeoxyglucose-positron emission tomography. In contrast, temporarily immunosuppressed allogeneic mice, following cessation of tacrolimus injection displayed diminished progression of the teratocarcinoma, accompanied by an accumulation of CD4/CD8-positive T cells, and finally achieved complete elimination of the teratocarcinoma. Our results indicated that malignant teratocarcinomas arising from induced pluripotent stem cell-derived cardiac tissue constructs provoked T cell-related host immune rejection to arrest tumour growth in murine allogeneic transplantation models.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biopsy
  • Cell Line
  • Cell Transformation, Neoplastic*
  • Fluorodeoxyglucose F18
  • Gene Order
  • Genetic Vectors / genetics
  • Graft Rejection / immunology*
  • Immunocompromised Host
  • Immunosuppressive Agents / administration & dosage
  • Induced Pluripotent Stem Cells* / cytology
  • Induced Pluripotent Stem Cells* / metabolism
  • Male
  • Mice
  • Mice, Transgenic
  • Models, Animal
  • Myocytes, Cardiac / cytology
  • Myocytes, Cardiac / pathology*
  • Positron-Emission Tomography
  • Stem Cell Transplantation / adverse effects*
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • Tacrolimus / administration & dosage
  • Teratocarcinoma / diagnosis
  • Teratocarcinoma / etiology*
  • Teratocarcinoma / pathology*
  • Transplantation, Homologous

Substances

  • Immunosuppressive Agents
  • Fluorodeoxyglucose F18
  • Tacrolimus