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

Deuse T, Wang D, Stubbendorff M, Itagaki R, Grabosch A, Greaves LC, Alawi M, Gruenewald A, Hu X, Hua X, Velden J, Reichenspurner H, Robbins RC, Jaenisch R, Weissman IL, Schrepfer S (2015)

Publication Type: Journal article

Publication year: 2015

Journal

Cell Stem Cell Elsevier (Cell Press)

Book Volume: 16

Pages Range: 33-8

Journal Issue: 1

DOI: 10.1016/j.stem.2014.11.003

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.

Involved external institutions

Stanford University US United States (USA) (US) Newcastle University GB United Kingdom (GB) Universitätsklinikum Hamburg-Eppendorf (UKE) DE Germany (DE) Massachusetts Institute of Technology (MIT) US United States (USA) (US)

How to cite

APA:

Deuse, T., Wang, D., Stubbendorff, M., Itagaki, R., Grabosch, A., Greaves, L.C.,... Schrepfer, S. (2015). SCNT-derived ESCs with mismatched mitochondria trigger an immune response in allogeneic hosts. Cell Stem Cell, 16(1), 33-8. https://doi.org/10.1016/j.stem.2014.11.003

MLA:

Deuse, Tobias, et al. "SCNT-derived ESCs with mismatched mitochondria trigger an immune response in allogeneic hosts." Cell Stem Cell 16.1 (2015): 33-8.

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