Approaching Thrombospondin-1 as a Potential Target for Mesenchymal Stromal Cells to Support Liver Regeneration after Partial Hepatectomy in Mouse and Humans

ORCID
0000-0003-2934-1880
Zugehörigkeit
Department of Visceral, Transplant, Thoracic and Vascular Surgery, University of Leipzig Medical Center, 04103 Leipzig, Germany;(L.T.);(M.C.);(P.S.);(S.N.);
Tietze, Lysann;
Zugehörigkeit
Department of Visceral, Transplant, Thoracic and Vascular Surgery, University of Leipzig Medical Center, 04103 Leipzig, Germany;(L.T.);(M.C.);(P.S.);(S.N.);
Christ, Madlen;
Zugehörigkeit
Klinik für Allgemein-, Viszeral- und Thoraxchirurgie, Helios Park-Klinikum Leipzig, 04289 Leipzig, Germany;(J.Y.);(M.B.)
Yu, Jiyeon;
ORCID
0000-0002-9208-8411
Zugehörigkeit
Department of Visceral, Transplant, Thoracic and Vascular Surgery, University of Leipzig Medical Center, 04103 Leipzig, Germany;(L.T.);(M.C.);(P.S.);(S.N.);
Stock, Peggy;
Zugehörigkeit
Department of Visceral, Transplant, Thoracic and Vascular Surgery, University of Leipzig Medical Center, 04103 Leipzig, Germany;(L.T.);(M.C.);(P.S.);(S.N.);
Nickel, Sandra;
Zugehörigkeit
Department of Visceral, Transplant, Thoracic and Vascular Surgery, University of Leipzig Medical Center, 04103 Leipzig, Germany;(L.T.);(M.C.);(P.S.);(S.N.);
Schulze, Annelie;
Zugehörigkeit
Klinik für Allgemein-, Viszeral- und Thoraxchirurgie, Helios Park-Klinikum Leipzig, 04289 Leipzig, Germany;(J.Y.);(M.B.)
Bartels, Michael;
Zugehörigkeit
Department of Visceral, Transplant, Thoracic and Vascular Surgery, University of Leipzig Medical Center, 04103 Leipzig, Germany;(L.T.);(M.C.);(P.S.);(S.N.);
Tautenhahn, Hans-Michael;
GND
1192515196
ORCID
0000-0001-8213-9548
Zugehörigkeit
Department of Visceral, Transplant, Thoracic and Vascular Surgery, University of Leipzig Medical Center, 04103 Leipzig, Germany;(L.T.);(M.C.);(P.S.);(S.N.);
Christ, Bruno

Extended liver resection carries the risk of post-surgery liver failure involving thrombospondin-1-mediated aggravation of hepatic epithelial plasticity and function. Mesenchymal stromal cells (MSCs), by interfering with thrombospondin-1 (THBS1), counteract hepatic dysfunction, though the mechanisms involved remain unknown. Herein, two-thirds partial hepatectomy in mice increased hepatic THBS1, downstream transforming growth factor-β3, and perturbation of liver tissue homeostasis. All these events were ameliorated by hepatic transfusion of human bone marrow-derived MSCs. Treatment attenuated platelet and macrophage recruitment to the liver, both major sources of THBS1. By mitigating THBS1, MSCs muted surgery-induced tissue deterioration and dysfunction, and thus supported post-hepatectomy regeneration. After liver surgery, patients displayed increased tissue THBS1, which is associated with functional impairment and may indicate a higher risk of post-surgery complications. Since liver dysfunction involving THBS1 improves with MSC treatment in various animal models, it seems feasible to also modulate THBS1 in humans to impede post-surgery acute liver failure.

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