Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Rong, Z; Wang, M; Hu, Z; Stradner, M; Zhu, S; Kong, H; Yi, H; Goldrath, A; Yang, YG; Xu, Y; Fu, X.
An effective approach to prevent immune rejection of human ESC-derived allografts.
Cell Stem Cell. 2014; 14(1):121-130
Doi: 10.1016/j.stem.2013.11.014
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- Co-Autor*innen der Med Uni Graz
- Stradner Martin Helmut
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- Abstract:
- Human embryonic stem cells (hESCs) hold great promise for cell therapy as a source of diverse differentiated cell types. One key bottleneck to realizing such potential is allogenic immune rejection of hESC-derived cells by recipients. Here, we optimized humanized mice (Hu-mice) reconstituted with a functional human immune system that mounts a vigorous rejection of hESCs and their derivatives. We established knockin hESCs that constitutively express CTLA4-Ig and PD-L1 before and after differentiation, denoted CP hESCs. We then demonstrated that allogenic CP hESC-derived teratomas, fibroblasts, and cardiomyocytes are immune protected in Hu-mice, while cells derived from parental hESCs are effectively rejected. Expression of both CTLA4-Ig, which disrupts T cell costimulatory pathways, and PD-L1, which activates T cell inhibitory pathway, is required to confer immune protection, as neither was sufficient on their own. These findings are instrumental for developing a strategy to protect hESC-derived cells from allogenic immune responses without requiring systemic immune suppression. Copyright © 2014 Elsevier Inc. All rights reserved.
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