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

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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.

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Author and article information

Journal

Journal ID (iso-abbrev): Cell Stem Cell

Title: Cell stem cell

ISSN (Electronic): 1875-9777

ISSN (Print): 1875-9777

Publication date (Electronic): Jan 8 2015

Volume: 16

Issue: 1

Affiliations

[1 ] TSI Laboratory, University Heart Center Hamburg, Martinistrasse 52, 20246 Hamburg, Germany; Cardiovascular Research Center Hamburg (CVRC) and DZHK (German Center for Cardiovascular Research), partner site Hamburg/Kiel/Luebeck, Martinistrasse 52, 20246 Hamburg, Germany; Cardiovascular Surgery, University Heart Center Hamburg, Martinistrasse 52, 20246 Hamburg, Germany.

[2 ] TSI Laboratory, University Heart Center Hamburg, Martinistrasse 52, 20246 Hamburg, Germany; Cardiovascular Research Center Hamburg (CVRC) and DZHK (German Center for Cardiovascular Research), partner site Hamburg/Kiel/Luebeck, Martinistrasse 52, 20246 Hamburg, Germany.

[3 ] Newcastle University Centre for Brain Ageing and Vitality, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK.

[4 ] Bioinformatics Service Facility, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany; Heinrich-Pette Institute, Leibniz Institute for Experimental Virology, Virus Genomics, Martinistrasse 52, 20246 Hamburg, Germany.

[5 ] Wellcome Trust Centre for Mitochondrial Research, Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK.

[6 ] Department of Nephropathology, Institute of Pathology, University Hospital Erlangen, Maximiliansplatz 2, 91054 Erlangen, Germany.

[7 ] Cardiovascular Research Center Hamburg (CVRC) and DZHK (German Center for Cardiovascular Research), partner site Hamburg/Kiel/Luebeck, Martinistrasse 52, 20246 Hamburg, Germany; Cardiovascular Surgery, University Heart Center Hamburg, Martinistrasse 52, 20246 Hamburg, Germany.

[8 ] Stanford Cardiovascular Institute and Department of Cardiothoracic Surgery, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305, USA.

[9 ] Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, 9 Cambridge Center, Cambridge, MA 02142, USA.

[10 ] Department of Developmental Biology, Stanford Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305, USA.

[11 ] TSI Laboratory, University Heart Center Hamburg, Martinistrasse 52, 20246 Hamburg, Germany; Cardiovascular Research Center Hamburg (CVRC) and DZHK (German Center for Cardiovascular Research), partner site Hamburg/Kiel/Luebeck, Martinistrasse 52, 20246 Hamburg, Germany; Stanford Cardiovascular Institute and Department of Cardiothoracic Surgery, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305, USA. Electronic address: schrepfer@stanford.edu.

Article

Publisher Item ID: S1934-5909(14)00515-3

DOI: 10.1016/j.stem.2014.11.003

PubMed ID: 25465116

SO-VID: 2d8a40a6-9424-460e-b908-7ed100e6dabf

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