Repair of acute liver damage with immune evasive hESC derived hepato-blasts.
CTLA-4-Ig
Human embryonic stem cells
Immune evasive
Liver damage
PD-L1
Journal
Stem cell research
ISSN: 1876-7753
Titre abrégé: Stem Cell Res
Pays: England
ID NLM: 101316957
Informations de publication
Date de publication:
12 2020
12 2020
Historique:
received:
21
06
2020
revised:
23
08
2020
accepted:
21
09
2020
pubmed:
5
10
2020
medline:
22
6
2021
entrez:
4
10
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33011360
pii: S1873-5061(20)30311-1
doi: 10.1016/j.scr.2020.102010
pii:
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
102010Informations de copyright
Copyright © 2020. Published by Elsevier B.V.