Intraportally delivered stem cell spheroids localize in the liver and protect hepatocytes against GalN/LPS-induced fulminant hepatic toxicity.
Animals
Cell Culture Techniques
Cell Survival
Dinoprostone
/ metabolism
Disease Models, Animal
Galactosamine
/ toxicity
Heme Oxygenase-1
/ metabolism
Interleukin-10
/ blood
Lipopolysaccharides
/ toxicity
Liver
/ metabolism
Liver Failure, Acute
/ pathology
Mesenchymal Stem Cell Transplantation
Mesenchymal Stem Cells
/ cytology
Mice
Mice, Nude
Oxidative Stress
Reactive Oxygen Species
/ metabolism
Superoxide Dismutase
/ metabolism
2D-cultured cells
Fulminant hepatic failure
Intraportal delivery
Mesenchymal stem cell
Spheroids
Journal
Stem cell research & therapy
ISSN: 1757-6512
Titre abrégé: Stem Cell Res Ther
Pays: England
ID NLM: 101527581
Informations de publication
Date de publication:
16 10 2019
16 10 2019
Historique:
received:
27
01
2019
accepted:
11
07
2019
revised:
29
04
2019
entrez:
17
10
2019
pubmed:
17
10
2019
medline:
17
7
2020
Statut:
epublish
Résumé
Systemic inflammatory response syndrome (SIRS) is common in severe fulminant hepatic failure (FHF) and has a high mortality rate (20-50%) due to irreversible cerebral edema or sepsis. Stem cell-based treatment has emerged as a promising alternative therapeutic strategy to prolong the survival of patients suffering from FHF via the inhibition of SIRS due to their immunomodulatory effects. 3D spheroids of adipose-derived mesenchymal stem cells (3D-ADSC) were prepared by the hanging drop method. The efficacy of the 3D-ADSC to rescue FHF was evaluated in a D-galactosamine/lipopolysaccharide (GalN/LPS)-induced mouse model of FHF via intraportal transplantation of the spheroids. Intraportally delivered 3D-ADSC better engrafted and localized into the damaged livers compared to 2D-cultured adipose-derived mesenchymal stem cells (2D-ADSC). Transplantation of 3D-ADSC rescued 50% of mice from FHF-induced lethality, whereas only 20% of mice survived when 2D-ADSC were transplanted. The improved transplantation outcomes correlated with the enhanced immunomodulatory effect of 3D-ADSC in the liver microenvironment. The study shows that the transplantation of optimized 3D-ADSC can efficiently ameliorate GalN/LPS-induced FHF due to improved viability, resistance to exogenous ROS, and enhanced immunomodulatory effects of 3D-ADSC.
Sections du résumé
BACKGROUND
Systemic inflammatory response syndrome (SIRS) is common in severe fulminant hepatic failure (FHF) and has a high mortality rate (20-50%) due to irreversible cerebral edema or sepsis. Stem cell-based treatment has emerged as a promising alternative therapeutic strategy to prolong the survival of patients suffering from FHF via the inhibition of SIRS due to their immunomodulatory effects.
METHODS
3D spheroids of adipose-derived mesenchymal stem cells (3D-ADSC) were prepared by the hanging drop method. The efficacy of the 3D-ADSC to rescue FHF was evaluated in a D-galactosamine/lipopolysaccharide (GalN/LPS)-induced mouse model of FHF via intraportal transplantation of the spheroids.
RESULTS
Intraportally delivered 3D-ADSC better engrafted and localized into the damaged livers compared to 2D-cultured adipose-derived mesenchymal stem cells (2D-ADSC). Transplantation of 3D-ADSC rescued 50% of mice from FHF-induced lethality, whereas only 20% of mice survived when 2D-ADSC were transplanted. The improved transplantation outcomes correlated with the enhanced immunomodulatory effect of 3D-ADSC in the liver microenvironment.
CONCLUSION
The study shows that the transplantation of optimized 3D-ADSC can efficiently ameliorate GalN/LPS-induced FHF due to improved viability, resistance to exogenous ROS, and enhanced immunomodulatory effects of 3D-ADSC.
Identifiants
pubmed: 31615539
doi: 10.1186/s13287-019-1337-3
pii: 10.1186/s13287-019-1337-3
pmc: PMC6794806
doi:
Substances chimiques
Lipopolysaccharides
0
Reactive Oxygen Species
0
Interleukin-10
130068-27-8
Galactosamine
7535-00-4
Heme Oxygenase-1
EC 1.14.14.18
Superoxide Dismutase
EC 1.15.1.1
superoxide dismutase 2
EC 1.15.1.1
Dinoprostone
K7Q1JQR04M
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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