Approaching Thrombospondin-1 as a Potential Target for Mesenchymal Stromal Cells to Support Liver Regeneration after Partial Hepatectomy in Mouse and Humans
Lysann Tietze,
Madlen Christ,
Jiyeon Yu,
Peggy Stock,
Sandra Nickel,
Annelie Schulze,
Michael Bartels,
Hans-Michael Tautenhahn,
Bruno Christ
Affiliations
Lysann Tietze
Department of Visceral, Transplant, Thoracic and Vascular Surgery, University of Leipzig Medical Center, 04103 Leipzig, Germany
Madlen Christ
Department of Visceral, Transplant, Thoracic and Vascular Surgery, University of Leipzig Medical Center, 04103 Leipzig, Germany
Jiyeon Yu
Klinik für Allgemein-, Viszeral- und Thoraxchirurgie, Helios Park-Klinikum Leipzig, 04289 Leipzig, Germany
Peggy Stock
Department of Visceral, Transplant, Thoracic and Vascular Surgery, University of Leipzig Medical Center, 04103 Leipzig, Germany
Sandra Nickel
Department of Visceral, Transplant, Thoracic and Vascular Surgery, University of Leipzig Medical Center, 04103 Leipzig, Germany
Annelie Schulze
Department of Visceral, Transplant, Thoracic and Vascular Surgery, University of Leipzig Medical Center, 04103 Leipzig, Germany
Michael Bartels
Klinik für Allgemein-, Viszeral- und Thoraxchirurgie, Helios Park-Klinikum Leipzig, 04289 Leipzig, Germany
Hans-Michael Tautenhahn
Department of Visceral, Transplant, Thoracic and Vascular Surgery, University of Leipzig Medical Center, 04103 Leipzig, Germany
Bruno Christ
Department of Visceral, Transplant, Thoracic and Vascular Surgery, University of Leipzig Medical Center, 04103 Leipzig, Germany
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.