title: Implantation of healthy matrix-embedded endothelial cells rescues dysfunctional endothelium and ischaemic tissue in liver engraftment.
abstract: Liver transplantation is limited by ischaemic injury which promotes endothelial cell and hepatocyte dysfunction and eventually organ failure. We sought to understand how endothelial state determines liver recovery after hepatectomy and engraftment.
  
  
  
  Matrix-embedded endothelial cells (MEECs) with retained healthy phenotype or control acellular matrices were implanted in direct contact with the remaining median lobe of donor mice undergoing partial hepatectomy (70%), or in the interface between the remaining median lobe and an autograft or isograft from the left lobe in hepatectomised recipient mice. Hepatic vascular architecture, DNA fragmentation and apoptosis in the median lobe and grafts, serum markers of liver damage and phenotype of macrophage and lymphocyte subsets in the liver after engraftment were analysed 7 days post-op.
  
  
  
  Healthy MEECs create a functional vascular splice in donor and recipient liver after 70% hepatectomy in mouse protecting these livers from ischaemic injury, hepatic congestion and inflammation. Macrophages recruited adjacent to the vascular nodes into the implants switched to an anti-inflammatory and regenerative profile M2. MEECs improved liver function and the rate of liver regeneration and prevented apoptosis in donor liver lobes, autologous grafts and syngeneic engraftment.
  
  
  
  Implants with healthy endothelial cells rescue liver donor and recipient endothelium and parenchyma from ischaemic injury after major hepatectomy and engraftment. This study highlights endothelial-hepatocyte crosstalk in hepatic repair and provides a promising new approach to improve regenerative medicine outcomes and liver transplantation.
authors: Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors: Pedro
authors: P
authors: Melgar-Lesmes
authors: Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.|Bioengineering Department, Institut Químic de Sarrià, Ramon Llull Univ, Barcelona, Spain.
authors: Mercedes
authors: M
authors: Balcells
authors: Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.|Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors: Elazer R
authors: ER
authors: Edelman
mesh_terms: D000818:Animals; D001119:Arginase / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000637:transplantation*; D004730:Endothelium, Vascular / Q000502:physiology; D015870:Gene Expression; D006498:Hepatectomy; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000098:blood supply*; D008115:Liver Regeneration; D016031:Liver Transplantation; D008264:Macrophages / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D011971:Receptors, Immunologic; D015427:Reperfusion Injury / Q000517:prevention & control*; D018418:Th2 Cells / Q000378:metabolism; D000637:Transaminases / Q000097:blood; D015854:Up-Regulation
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; C581013:MRC1 protein, mouse; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; C413576:Retnla protein, mouse; D000637:Transaminases; C544448:Arg1 protein, mouse; D001119:Arginase
keywords: ENDOTHELIAL CELLS; ISCHAEMIA; LIVER IMMUNOLOGY; LIVER REGENERATION