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 journal › SCORING: Journal article › Research › peer-review
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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 -