SCNT-derived ESCs with mismatched mitochondria trigger an immune response in allogeneic hosts

Tobias Deuse, Dong Wang, Mandy Stubbendorff, Ryo Itagaki, Antje Grabosch, Laura C. Greaves, Malik Alawi, Anne Grünewald, Xiaomeng Hu, Xiaoqin Hua, Joachim Velden, Hermann Reichenspurner, Robert C. Robbins, Rudolf Jaenisch, Irving L. Weissman, Sonja Schrepfer

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

The generation of pluripotent stem cells by somatic cell nuclear transfer (SCNT) has recently been achieved in human cells and sparked new interest in this technology. The authors reporting this methodical breakthrough speculated that SCNT would allow the creation of patient-matched embryonic stem cells, even in patients with hereditary mitochondrial diseases. However, herein we show that mismatched mitochondria in nuclear-transfer-derived embryonic stem cells (NT-ESCs) possess alloantigenicity and are subject to immune rejection. In a murine transplantation setup, we demonstrate that allogeneic mitochondria in NT-ESCs, which are nucleus-identical to the recipient, may trigger an adaptive alloimmune response that impairs the survival of NT-ESC grafts. The immune response is adaptive, directed against mitochondrial content, and amenable for tolerance induction. Mitochondrial alloantigenicity should therefore be considered when developing therapeutic SCNT-based strategies.

Original languageEnglish (US)
Pages (from-to)33-38
Number of pages6
JournalCell Stem Cell
Volume16
Issue number1
DOIs
StatePublished - Jan 8 2015
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Cell Biology

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