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Tytuł:
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Repair of acute liver damage with immune evasive hESC derived hepato-blasts.
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Autorzy:
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Liu J; Cancer Research Institute, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong 510515, China.
Pan T; Institute of Public Health, Guangzhou Institutes of Biomedicine and Health (GIBH), Chinese Academy of Sciences, Guangzhou 510530, China; University of Chinese Academy of Science, Beijing 100049, China; Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China; Guangdong Provincial Key Laboratory of Biocomputing, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
Chen Y; Institute of Public Health, Guangzhou Institutes of Biomedicine and Health (GIBH), Chinese Academy of Sciences, Guangzhou 510530, China; Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China; Guangdong Provincial Key Laboratory of Biocomputing, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
Liu Y; Institute of Public Health, Guangzhou Institutes of Biomedicine and Health (GIBH), Chinese Academy of Sciences, Guangzhou 510530, China; University of Chinese Academy of Science, Beijing 100049, China; Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China; Guangdong Provincial Key Laboratory of Biocomputing, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
Yang F; Institute of Public Health, Guangzhou Institutes of Biomedicine and Health (GIBH), Chinese Academy of Sciences, Guangzhou 510530, China; Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China; Guangdong Provincial Key Laboratory of Biocomputing, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
Chen Q; Cancer Research Institute, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong 510515, China.
Abbas N; Institute of Public Health, Guangzhou Institutes of Biomedicine and Health (GIBH), Chinese Academy of Sciences, Guangzhou 510530, China; University of Chinese Academy of Science, Beijing 100049, China; Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China; Guangdong Provincial Key Laboratory of Biocomputing, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
Zhong M; Cancer Research Institute, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong 510515, China.
Zhang Q; Cancer Research Institute, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong 510515, China.
Xu Y; Cancer Research Institute, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong 510515, China; Division of Biological Sciences, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA. Electronic address: .
Li YX; Institute of Public Health, Guangzhou Institutes of Biomedicine and Health (GIBH), Chinese Academy of Sciences, Guangzhou 510530, China; University of Chinese Academy of Science, Beijing 100049, China; Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China; Guangdong Provincial Key Laboratory of Biocomputing, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China; Guangzhou Regenerative Medicine and Health Guangdong Laboratory, 510005 Guangzhou, China. Electronic address: li_yinxiong_.
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Źródło:
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Stem cell research [Stem Cell Res] 2020 Dec; Vol. 49, pp. 102010. Date of Electronic Publication: 2020 Sep 26.
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Typ publikacji:
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Journal Article; Research Support, Non-U.S. Gov't
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Język:
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English
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Imprint Name(s):
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Original Publication: Kidlington, Oxford : Elsevier
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MeSH Terms:
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Human Embryonic Stem Cells*
Animals ; Cell Differentiation ; Cell- and Tissue-Based Therapy ; Embryonic Stem Cells ; Hepatocytes ; Liver ; Mice
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Contributed Indexing:
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Keywords: CTLA-4-Ig; Human embryonic stem cells; Immune evasive; Liver damage; PD-L1
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Entry Date(s):
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Date Created: 20201004 Date Completed: 20210621 Latest Revision: 20210621
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Update Code:
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20240105
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DOI:
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10.1016/j.scr.2020.102010
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PMID:
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33011360
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Human embryonic stem cells (hESCs) can undergo unlimited self-renewal and differentiate into hepatic cells, including expandable hepato-blasts (HBs) and hepatocyte-like cells (HLCs) in vitro. Therefore, hESC-derived HBs have the potential to become a renewable cell source for cell therapy of serious liver damage. However, one of the key challenges for such cell therapy is the allogeneic immune rejection of hESC-derived HBs. To overcome this challenge, we developed a strategy to protect the hESC-derived HBs from allogeneic immune rejection by ectopically expressing immune suppressive molecules CTLA4-Ig and PD-L1, denoted CP HBs. Like HBs derived from normal hESCs, CP HBs are capable of repairing liver damage in animal models. Using humanized mice (Hu-mice) reconstituted with human immune system, we showed that CP HBs are protected from allogeneic immune system and can survive long-term in Hu-mice. These data support the feasibility to develop CP HBs into a cell therapy to treat serious liver damage.
(Copyright © 2020. Published by Elsevier B.V.)
