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SCNT-Derived ESCs with Mismatched Mitochondria Trigger an Immune Response in Allogeneic Hosts

Lookup NU author(s): Dr Laura Greaves, Dr Anne Grunewald



This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).


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.

Publication metadata

Author(s): Deuse T, Wang D, Stubbendorff M, Itagaki R, Grabosch A, Greaves LC, Alawi M, Grunewald A, Hu XM, Hua XQ, Velden J, Reichenspurner H, Robbins RC, Jaenisch R, Weissman IL, Schrepfer S

Publication type: Article

Publication status: Published

Journal: Cell Stem Cell

Year: 2015

Volume: 16

Issue: 1

Pages: 33-38

Print publication date: 08/01/2015

Online publication date: 20/11/2014

Acceptance date: 07/11/2014

Date deposited: 18/12/2015

ISSN (print): 1934-5909

ISSN (electronic): 1875-9777

Publisher: Cell Press


DOI: 10.1016/j.stem.2014.11.003


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Funder referenceFunder name
DFG: SCHR992/3-1German Research Foundation (Deutsche Forschungsgemeinschaft)
CDA 2013-2015Fondation Leducq
SCHR992/4-1German Research Foundation (Deutsche Forschungsgemeinschaft)