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Human Mesenchymal Stromal Cells Resolve Lipid Load in High Fat Diet-Induced Non-Alcoholic Steatohepatitis in Mice by Mitochondria Donation

GND
118066242
Zugehörigkeit
Division of General, Visceral and Vascular Surgery, University Hospital Jena, 07747 Jena, Germany
Nickel, Sandra;
Zugehörigkeit
Department of Visceral, Transplant, Thoracic and Vascular Surgery, University of Leipzig Medical Center, 04103 Leipzig, Germany;(S.N.);(M.C.);(S.S.);(J.K.);(H.K.);(L.T.);(I.B.);(M.-J.H.);(P.S.)
Christ, Madlen;
Zugehörigkeit
Department of Visceral, Transplant, Thoracic and Vascular Surgery, University of Leipzig Medical Center, 04103 Leipzig, Germany;(S.N.);(M.C.);(S.S.);(J.K.);(H.K.);(L.T.);(I.B.);(M.-J.H.);(P.S.)
Schmidt, Sandra;
GND
136721532
ORCID
0000-0003-0177-836X
Zugehörigkeit
Department of Visceral, Transplant, Thoracic and Vascular Surgery, University of Leipzig Medical Center, 04103 Leipzig, Germany;(S.N.);(M.C.);(S.S.);(J.K.);(H.K.);(L.T.);(I.B.);(M.-J.H.);(P.S.)
Kosacka, Joanna;
Zugehörigkeit
Department of Visceral, Transplant, Thoracic and Vascular Surgery, University of Leipzig Medical Center, 04103 Leipzig, Germany;(S.N.);(M.C.);(S.S.);(J.K.);(H.K.);(L.T.);(I.B.);(M.-J.H.);(P.S.)
Kühne, Hagen;
GND
123882958
ORCID
0000-0002-3232-1277
Zugehörigkeit
Department of Gastroenterology, Justus-Liebig-University, 35392 Giessen, Germany;(M.R.);(E.R.)
Roderfeld, Martin;
GND
128494514
ORCID
0000-0001-8888-1030
Zugehörigkeit
Institute of Pathology, Heidelberg University Hospital, 69120 Heidelberg, Germany;
Longerich, Thomas;
GND
1163284823
ORCID
0000-0003-2934-1880
Zugehörigkeit
Department of Visceral, Transplant, Thoracic and Vascular Surgery, University of Leipzig Medical Center, 04103 Leipzig, Germany;(S.N.);(M.C.);(S.S.);(J.K.);(H.K.);(L.T.);(I.B.);(M.-J.H.);(P.S.)
Tietze, Lysann;
Zugehörigkeit
Department of Visceral, Transplant, Thoracic and Vascular Surgery, University of Leipzig Medical Center, 04103 Leipzig, Germany;(S.N.);(M.C.);(S.S.);(J.K.);(H.K.);(L.T.);(I.B.);(M.-J.H.);(P.S.)
Bosse, Ina;
Zugehörigkeit
Department of Visceral, Transplant, Thoracic and Vascular Surgery, University of Leipzig Medical Center, 04103 Leipzig, Germany;(S.N.);(M.C.);(S.S.);(J.K.);(H.K.);(L.T.);(I.B.);(M.-J.H.);(P.S.)
Hsu, Mei-Ju;
GND
1230495231
ORCID
0000-0002-9208-8411
Zugehörigkeit
Department of Visceral, Transplant, Thoracic and Vascular Surgery, University of Leipzig Medical Center, 04103 Leipzig, Germany;(S.N.);(M.C.);(S.S.);(J.K.);(H.K.);(L.T.);(I.B.);(M.-J.H.);(P.S.)
Stock, Peggy;
GND
172334829
ORCID
0000-0001-5739-5400
Zugehörigkeit
Department of Gastroenterology, Justus-Liebig-University, 35392 Giessen, Germany;(M.R.);(E.R.)
Roeb, Elke;
GND
1192515196
ORCID
0000-0001-8213-9548
Zugehörigkeit
Department of Visceral, Transplant, Thoracic and Vascular Surgery, University of Leipzig Medical Center, 04103 Leipzig, Germany;(S.N.);(M.C.);(S.S.);(J.K.);(H.K.);(L.T.);(I.B.);(M.-J.H.);(P.S.)
Christ, Bruno

Mesenchymal stromal cells (MSC) increasingly emerge as an option to ameliorate non-alcoholic steatohepatitis (NASH), a serious disease, which untreated may progress to liver cirrhosis and cancer. Before clinical translation, the mode of action of MSC needs to be established. Here, we established NASH in an immune-deficient mouse model by feeding a high fat diet. Human bone-marrow-derived MSC were delivered to the liver via intrasplenic transplantation. As verified by biochemical and image analyses, human mesenchymal stromal cells improved high-fat-diet-induced NASH in the mouse liver by decreasing hepatic lipid content and inflammation, as well as by restoring tissue homeostasis. MSC-mediated changes in gene expression indicated the switch from lipid storage to lipid utilization. It was obvious that host mouse hepatocytes harbored human mitochondria. Thus, it is feasible that resolution of NASH in mouse livers involved the donation of human mitochondria to the mouse hepatocytes. Therefore, human MSC might provide oxidative capacity for lipid breakdown followed by restoration of metabolic and tissue homeostasis.

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Einordnung

Herausgeber(in):
Fiorucci, Stefano
Erschienen in:
Cells : open access journal
Bd. 11, 2022, H. 11 (02.06.2022)Art.-Nr.:1829, S. 1-21
Band:
11, 2022
Heft:
11
Datum der Veröffentlichung:
02.06.2022
DOI:
10.3390/cells11111829
Sprache:
Englisch
Ressourcentyp:
Text
Umfang:
21 Seiten
Erscheinungsort:
Basel
Verlag:
MDPI
Schlagwörter:
mesenchymal stromal cells; non-alcoholic steatohepatitis; cell transplantation; mitochondria transfer
DDC-Sachgruppe der DNB:
610 Medizin, Gesundheit
Einrichtung:
Friedrich-Schiller-Universität Jena, Medizinische Fakultät

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