Mesenchymal stromal cells mitigate liver damage after extended resection in the pig by modulating thrombospondin-1/TGF-β.
Journal
NPJ Regenerative medicine
ISSN: 2057-3995
Titre abrégé: NPJ Regen Med
Pays: United States
ID NLM: 101699846
Informations de publication
Date de publication:
03 Dec 2021
03 Dec 2021
Historique:
received:
09
06
2021
accepted:
01
11
2021
entrez:
4
12
2021
pubmed:
5
12
2021
medline:
5
12
2021
Statut:
epublish
Résumé
Post-surgery liver failure is a serious complication for patients after extended partial hepatectomies (ePHx). Previously, we demonstrated in the pig model that transplantation of mesenchymal stromal cells (MSC) improved circulatory maintenance and supported multi-organ functions after 70% liver resection. Mechanisms behind the beneficial MSC effects remained unknown. Here we performed 70% liver resection in pigs with and without MSC treatment, and animals were monitored for 24 h post surgery. Gene expression profiles were determined in the lung and liver. Bioinformatics analysis predicted organ-independent MSC targets, importantly a role for thrombospondin-1 linked to transforming growth factor-β (TGF-β) and downstream signaling towards providing epithelial plasticity and epithelial-mesenchymal transition (EMT). This prediction was supported histologically and mechanistically, the latter with primary hepatocyte cell cultures. MSC attenuated the surgery-induced increase of tissue damage, of thrombospondin-1 and TGF-β, as well as of epithelial plasticity in both the liver and lung. This suggests that MSC ameliorated surgery-induced hepatocellular stress and EMT, thus supporting epithelial integrity and facilitating regeneration. MSC-derived soluble factor(s) did not directly interfere with intracellular TGF-β signaling, but inhibited thrombospondin-1 secretion from thrombocytes and non-parenchymal liver cells, therewith obviously reducing the availability of active TGF-β.
Identifiants
pubmed: 34862411
doi: 10.1038/s41536-021-00194-4
pii: 10.1038/s41536-021-00194-4
pmc: PMC8642541
doi:
Types de publication
Journal Article
Langues
eng
Pagination
84Subventions
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : CH 109/25-1
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : 436883643
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : DO 373-20/1
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : DO 373-19/1
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : TA 1583/1-1
Organisme : Bundesministerium für Bildung und Forschung (Federal Ministry of Education and Research)
ID : PTJ-031L0043
Organisme : Bundesministerium für Bildung und Forschung (Federal Ministry of Education and Research)
ID : PTJ-031L0043
Informations de copyright
© 2021. The Author(s).
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