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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
Affiliation
Division of General, Visceral and Vascular Surgery, University Hospital Jena, 07747 Jena, Germany
Nickel, Sandra;
Affiliation
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;
Affiliation
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
Affiliation
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;
Affiliation
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
Affiliation
Department of Gastroenterology, Justus-Liebig-University, 35392 Giessen, Germany;(M.R.);(E.R.)
Roderfeld, Martin;
GND
128494514
ORCID
0000-0001-8888-1030
Affiliation
Institute of Pathology, Heidelberg University Hospital, 69120 Heidelberg, Germany;
Longerich, Thomas;
GND
1163284823
ORCID
0000-0003-2934-1880
Affiliation
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;
Affiliation
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;
Affiliation
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
Affiliation
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
Affiliation
Department of Gastroenterology, Justus-Liebig-University, 35392 Giessen, Germany;(M.R.);(E.R.)
Roeb, Elke;
GND
1192515196
ORCID
0000-0001-8213-9548
Affiliation
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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Editor:
Fiorucci, Stefano
Published in:
Cells : open access journal
Vol. 11, 2022, No. 11 (02.06.2022)Art.-No.:1829, p. 1-21
Volume:
11, 2022
No.:
11
Date Issued:
02.06.2022
DOI:
10.3390/cells11111829
Language:
English
Type of Resource:
Text
Extent:
21 Seiten
Place Term:
Basel
Publisher:
MDPI
Keywords:
  1. mesenchymal stromal cells
    Typ
    Schlagwort
  1. non-alcoholic steatohepatitis
    Typ
    Schlagwort
  1. cell transplantation
    Typ
    Schlagwort
  1. mitochondria transfer
    Typ
    Schlagwort
DDC subject of DNB:
610 Medical sciences Medicine
Hosting institution:
Friedrich-Schiller-Universität Jena, Medizinische Fakultät

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License Holder: © 2022 by the authors.

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This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively.