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Lookup NU author(s): Professor Laura GreavesORCiD, 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.
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
URL: http://dx.doi.org/10.1016/j.stem.2014.11.003
DOI: 10.1016/j.stem.2014.11.003
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