Publication Details

Category Text Publication
Reference Category Journals
DOI 10.3390/biomedicines8090350
Licence creative commons licence
Title (Primary) Mitochondrial transfer by human mesenchymal stromal cells ameliorates hepatocyte lipid load in a mouse model of NASH
Author 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.
Source Titel Biomedicines
Year 2020
Department MOLSYB
Volume 8
Issue 9
Page From art. 350
Language englisch
Supplements https://www.mdpi.com/2227-9059/8/9/350/s1
Keywords non-alcoholic steatohepatitis (NASH); tunneling nanotubes (TNTs); primary hepatocytes; organelle transfer; mesenchymal stromal cells
UFZ wide themes Exposom;
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.
Persistent UFZ Identifier https://www.ufz.de/index.php?en=20939&ufzPublicationIdentifier=23762
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. (2020):
Mitochondrial transfer by human mesenchymal stromal cells ameliorates hepatocyte lipid load in a mouse model of NASH
Biomedicines 8 (9), art. 350