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Cited by 43Mesenchymal stem cell researchLiver Disease Diagnosis and TreatmentLiver physiology and pathology

Mitochondrial Transfer by Human Mesenchymal Stromal Cells Ameliorates Hepatocyte Lipid Load in a Mouse Model of NASH

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Hsu, Mei-Ju, Karkossa, Isabel, Schäfer, Ingo, Christ, Madlen, Kühne, Hagen, Schubert, Kristin, Rolle-Kampczyk, Ulrike E., Kalkhof, Stefan +4 more·2020·Biomedicines
DOI 10.3390/biomedicines8090350PMC PMC7554948
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Abstract

Mesenchymal stromal cell (MSC) transplantation ameliorated hepatic lipid load; tissue inflammation; and fibrosis in rodent animal models of non-alcoholic steatohepatitis (NASH) by as yet largely unknown mechanism(s). In a mouse model of NASH; we transplanted bone marrow-derived MSCs into the livers; which were analyzed one week thereafter. Combined metabolomic and proteomic data were applied to weighted gene correlation network analysis (WGCNA) and subsequent identification of key drivers. Livers were analyzed histologically and biochemically. The mechanisms of MSC action on hepatocyte lipid accumulation were studied in co-cultures of hepatocytes and MSCs by quantitative image analysis and immunocytochemistry. WGCNA and key driver analysis revealed that NASH caused the impairment of central carbon; amino acid; and lipid metabolism associated with mitochondrial and peroxisomal dysfunction; which was reversed by MSC treatment. MSC improved hepatic lipid metabolism and tissue homeostasis. In co-cultures of hepatocytes and MSCs; the decrease of lipid load was associated with the transfer of mitochondria from the MSCs to the hepatocytes via tunneling nanotubes (TNTs). Hence; MSCs may ameliorate lipid load and tissue perturbance by the donation of mitochondria to the hepatocytes. Thereby; they may provide oxidative capacity for lipid breakdown and thus promote recovery from NASH-induced metabolic impairment and tissue injury.

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Cited by

Sorted by citations

Authors
Hsu, M.-J., Karkossa, I., Schäfer, I., Christ, M., Kühne, H., Schubert, K., Rolle-Kampczyk, U. E., Kalkhof, S., Nickel, S., Seibel, P., von Bergen, M., & Christ, B.
Affiliations
  • University Hospital Leipzig (DE)
  • Helmholtz Centre for Environmental Research (DE)
  • Leipzig University (DE)
  • Department of Molecular Systems Biology, Helmholtz Centre for Environmental Research (UFZ), 04318 Leipzig, Germany
Corresponding author
Christ, Bruno
ORCID
Venue
Biomedicines
Publisher
MDPI AG
Published
2020-09-14
Volume
8
Issue
9
Pages
350
ISSN
2227-9059 (ISSN-L)
DOI
10.3390/biomedicines8090350
PMC
PMC7554948
OpenAlex
W3085480356
Cited by
43
References
8
Citations by year
2026: 10 · 2025: 8 · 2024: 6 · 2023: 6 · 2022: 8 · 2021: 4 · 2020: 1
FWCI
2.46
Type
journal article
Language
en
Open access
Licence
Locations
  • Biomedicines (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Publikationsdatenbank der Fraunhofer-Gesellschaft (Fraunhofer-Gesellschaft) (submittedVersion, other-oa)
  • Fraunhofer-Publica (Fraunhofer-Gesellschaft) (submittedVersion)
  • Qucosa (Saxon State and University Library Dresden) (submittedVersion, cc-by)
Funders
  • Deutsche Forschungsgemeinschaft (CH109/22-2)
  • Ministry of Science and Technology, Taiwan Postdoctoral Research Abroad Program (105-2917-I-564-071)
Topics
  • Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
  • Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
Keywords
nonalcoholic steatohepatitis, mesenchymal stem cells, mitochondrial transfer, hepatocyte lipid accumulation, tunneling nanotubes, mitochondrial dysfunction, peroxisomal dysfunction, hepatic lipid metabolism, liver fibrosis

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