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

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SCNT-derived ESCs with mismatched mitochondria trigger an immune response in allogeneic hosts. / Deuse, Tobias; Wang, Dong; Stubbendorff, Mandy; Itagaki, Ryo; Grabosch, Antje; Greaves, Laura C; Alawi, Malik; Grünewald, Anne; Hu, Xiaomeng; Hua, Xiaoqin; Velden, Joachim; Reichenspurner, Hermann; Robbins, Robert C; Jaenisch, Rudolf; Weissman, Irving L; Schrepfer, Sonja.

In: CELL STEM CELL, Vol. 16, No. 1, 08.01.2015, p. 33-38.

Research output: SCORING: Contribution to journalSCORING: Journal articleResearchpeer-review

Harvard

Deuse, T, Wang, D, Stubbendorff, M, Itagaki, R, Grabosch, A, Greaves, LC, Alawi, M, Grünewald, A, Hu, X, Hua, X, Velden, J, Reichenspurner, H, Robbins, RC, Jaenisch, R, Weissman, IL & Schrepfer, S 2015, 'SCNT-derived ESCs with mismatched mitochondria trigger an immune response in allogeneic hosts', CELL STEM CELL, vol. 16, no. 1, pp. 33-38. https://doi.org/10.1016/j.stem.2014.11.003

APA

Deuse, T., Wang, D., Stubbendorff, M., Itagaki, R., Grabosch, A., Greaves, L. C., Alawi, M., Grünewald, A., Hu, X., Hua, X., Velden, J., Reichenspurner, H., Robbins, R. C., Jaenisch, R., Weissman, I. L., & Schrepfer, S. (2015). SCNT-derived ESCs with mismatched mitochondria trigger an immune response in allogeneic hosts. CELL STEM CELL, 16(1), 33-38. https://doi.org/10.1016/j.stem.2014.11.003

Vancouver

Deuse T, Wang D, Stubbendorff M, Itagaki R, Grabosch A, Greaves LC et al. SCNT-derived ESCs with mismatched mitochondria trigger an immune response in allogeneic hosts. CELL STEM CELL. 2015 Jan 8;16(1):33-38. https://doi.org/10.1016/j.stem.2014.11.003

Bibtex

@article{ab0b3050365b41f7ad130ff6922370c7,
title = "SCNT-derived ESCs with mismatched mitochondria trigger an immune response in allogeneic hosts",
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.",
keywords = "Animals, Antigens, Embryonic Stem Cells, Humans, Immunity, Mice, Inbred BALB C, Mitochondria, Nuclear Transfer Techniques, Transplantation, Homologous",
author = "Tobias Deuse and Dong Wang and Mandy Stubbendorff and Ryo Itagaki and Antje Grabosch and Greaves, {Laura C} and Malik Alawi and Anne Gr{\"u}newald and Xiaomeng Hu and Xiaoqin Hua and Joachim Velden and Hermann Reichenspurner and Robbins, {Robert C} and Rudolf Jaenisch and Weissman, {Irving L} and Sonja Schrepfer",
note = "Copyright {\textcopyright} 2015 Elsevier Inc. All rights reserved.",
year = "2015",
month = jan,
day = "8",
doi = "10.1016/j.stem.2014.11.003",
language = "English",
volume = "16",
pages = "33--38",
journal = "CELL STEM CELL",
issn = "1934-5909",
publisher = "Cell Press",
number = "1",

}

RIS

TY - JOUR

T1 - SCNT-derived ESCs with mismatched mitochondria trigger an immune response in allogeneic hosts

AU - Deuse, Tobias

AU - Wang, Dong

AU - Stubbendorff, Mandy

AU - Itagaki, Ryo

AU - Grabosch, Antje

AU - Greaves, Laura C

AU - Alawi, Malik

AU - Grünewald, Anne

AU - Hu, Xiaomeng

AU - Hua, Xiaoqin

AU - Velden, Joachim

AU - Reichenspurner, Hermann

AU - Robbins, Robert C

AU - Jaenisch, Rudolf

AU - Weissman, Irving L

AU - Schrepfer, Sonja

N1 - Copyright © 2015 Elsevier Inc. All rights reserved.

PY - 2015/1/8

Y1 - 2015/1/8

N2 - 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.

AB - 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.

KW - Animals

KW - Antigens

KW - Embryonic Stem Cells

KW - Humans

KW - Immunity

KW - Mice, Inbred BALB C

KW - Mitochondria

KW - Nuclear Transfer Techniques

KW - Transplantation, Homologous

U2 - 10.1016/j.stem.2014.11.003

DO - 10.1016/j.stem.2014.11.003

M3 - SCORING: Journal article

C2 - 25465116

VL - 16

SP - 33

EP - 38

JO - CELL STEM CELL

JF - CELL STEM CELL

SN - 1934-5909

IS - 1

ER -