Mitochondrial Transfer by Human Mesenchymal Stromal Cells Ameliorates Hepatocyte Lipid Load in a Mouse Model of NASH
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;...
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MDPI AG
2020-09-01
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| Online Access: | https://www.mdpi.com/2227-9059/8/9/350 |
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| author | Mei-Ju Hsu Isabel Karkossa Ingo Schäfer Madlen Christ Hagen Kühne Kristin Schubert Ulrike E. Rolle-Kampczyk Stefan Kalkhof Sandra Nickel Peter Seibel Martin von Bergen Bruno Christ |
| author_facet | Mei-Ju Hsu Isabel Karkossa Ingo Schäfer Madlen Christ Hagen Kühne Kristin Schubert Ulrike E. Rolle-Kampczyk Stefan Kalkhof Sandra Nickel Peter Seibel Martin von Bergen Bruno Christ |
| author_sort | Mei-Ju Hsu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T16:20:27Z |
| format | Article |
| id | doaj.art-3b83bdaa32d64c15903233706de71b1f |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T16:20:27Z |
| publishDate | 2020-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-3b83bdaa32d64c15903233706de71b1f2023-11-20T13:43:07ZengMDPI AGBiomedicines2227-90592020-09-018935010.3390/biomedicines8090350Mitochondrial Transfer by Human Mesenchymal Stromal Cells Ameliorates Hepatocyte Lipid Load in a Mouse Model of NASHMei-Ju Hsu0Isabel Karkossa1Ingo Schäfer2Madlen Christ3Hagen Kühne4Kristin Schubert5Ulrike E. Rolle-Kampczyk6Stefan Kalkhof7Sandra Nickel8Peter Seibel9Martin von Bergen10Bruno Christ11Applied Molecular Hepatology Laboratory, Department of Visceral, Transplant, Thoracic and Vascular Surgery, University of Leipzig Medical Center, 04103 Leipzig, GermanyDepartment of Molecular Systems Biology, Helmholtz Centre for Environmental Research (UFZ), 04318 Leipzig, GermanyMolecular Cell Therapy, Center for Biotechnology and Biomedicine, Leipzig University, 04103 Leipzig, GermanyApplied Molecular Hepatology Laboratory, Department of Visceral, Transplant, Thoracic and Vascular Surgery, University of Leipzig Medical Center, 04103 Leipzig, GermanyApplied Molecular Hepatology Laboratory, Department of Visceral, Transplant, Thoracic and Vascular Surgery, University of Leipzig Medical Center, 04103 Leipzig, GermanyDepartment of Molecular Systems Biology, Helmholtz Centre for Environmental Research (UFZ), 04318 Leipzig, GermanyDepartment of Molecular Systems Biology, Helmholtz Centre for Environmental Research (UFZ), 04318 Leipzig, GermanyDepartment of Molecular Systems Biology, Helmholtz Centre for Environmental Research (UFZ), 04318 Leipzig, GermanyApplied Molecular Hepatology Laboratory, Department of Visceral, Transplant, Thoracic and Vascular Surgery, University of Leipzig Medical Center, 04103 Leipzig, GermanyMolecular Cell Therapy, Center for Biotechnology and Biomedicine, Leipzig University, 04103 Leipzig, GermanyDepartment of Molecular Systems Biology, Helmholtz Centre for Environmental Research (UFZ), 04318 Leipzig, GermanyApplied Molecular Hepatology Laboratory, Department of Visceral, Transplant, Thoracic and Vascular Surgery, University of Leipzig Medical Center, 04103 Leipzig, GermanyMesenchymal 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.https://www.mdpi.com/2227-9059/8/9/350non-alcoholic steatohepatitis (NASH)tunneling nanotubes (TNTs)primary hepatocytesorganelle transfermesenchymal stromal cells |
| spellingShingle | Mei-Ju Hsu Isabel Karkossa Ingo Schäfer Madlen Christ Hagen Kühne Kristin Schubert Ulrike E. Rolle-Kampczyk Stefan Kalkhof Sandra Nickel Peter Seibel Martin von Bergen Bruno Christ Mitochondrial Transfer by Human Mesenchymal Stromal Cells Ameliorates Hepatocyte Lipid Load in a Mouse Model of NASH Biomedicines non-alcoholic steatohepatitis (NASH) tunneling nanotubes (TNTs) primary hepatocytes organelle transfer mesenchymal stromal cells |
| title | Mitochondrial Transfer by Human Mesenchymal Stromal Cells Ameliorates Hepatocyte Lipid Load in a Mouse Model of NASH |
| title_full | Mitochondrial Transfer by Human Mesenchymal Stromal Cells Ameliorates Hepatocyte Lipid Load in a Mouse Model of NASH |
| title_fullStr | Mitochondrial Transfer by Human Mesenchymal Stromal Cells Ameliorates Hepatocyte Lipid Load in a Mouse Model of NASH |
| title_full_unstemmed | Mitochondrial Transfer by Human Mesenchymal Stromal Cells Ameliorates Hepatocyte Lipid Load in a Mouse Model of NASH |
| title_short | Mitochondrial Transfer by Human Mesenchymal Stromal Cells Ameliorates Hepatocyte Lipid Load in a Mouse Model of NASH |
| title_sort | mitochondrial transfer by human mesenchymal stromal cells ameliorates hepatocyte lipid load in a mouse model of nash |
| topic | non-alcoholic steatohepatitis (NASH) tunneling nanotubes (TNTs) primary hepatocytes organelle transfer mesenchymal stromal cells |
| url | https://www.mdpi.com/2227-9059/8/9/350 |
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