Blockade of cell adhesion molecules enhances cell engraftment in a murine model of liver cell transplantation

• Published in: Transplant immunology Vol. 35; pp. 7 - 11
• Main Authors: Alfaro, Javier, Pérez, Dolores, Jiménez, Carlos, Serrano, Manuel, Martínez-Flores, José Ángel, Grau, Montserrat, Sánchez-Zapardiel, Elena, Paz-Artal, Estela, Serrano, Antonio
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-03-2016
• Subjects: Adhesion molecules; Allergy and Immunology; Allografts; Animals; Antibodies - pharmacology; Disease Models, Animal; End Stage Liver Disease - immunology; End Stage Liver Disease - therapy; Engraftment; Graft Survival - drug effects; Graft Survival - immunology; Human Umbilical Vein Endothelial Cells - immunology; Humans; Integrin beta3 - immunology; Intercellular Adhesion Molecule-1 - immunology; Liver - immunology; Liver cell transplantation; Male; Mice; Stem Cell Transplantation; Vascular patency; orthotropic liver transplantation; intercellular adhesion molecule I; embryonic stem cells; MoAb; Vascular patency; LT; ICAM-1; CT; cell transplantation; OLT; liver cell transplantation; human umbilical vein endothelial cells; Engraftment; Adhesion molecules; LCT; liver transplantation; HUVECs; ESCs; monoclonal antibodies; Liver cell transplantation
• ISSN: 0966-3274; 1878-5492
• DOI: 10.1016/j.trim.2016.01.008

Abstract Aim OLT is the best alternative for patients with end-stage liver diseases. However, as the need for organs surpasses donor availability, alternatives to OLT are required. LCT could be a useful option versus OLT in several patients even though its low cell-engraftment hampers its efficiency. Endothelial cell barrier is the main obstacle for the implantation of cells into the parenchyma. Our study has focused on the modification of the endothelial barrier with monoclonal antibodies against adhesion molecules in order to increase cell engraftment in a mouse model of liver cell transplantation. Methods Anti-mouse CD54 and anti-mouse CD61 antibodies were administered intrasplenically to healthy mice within 60 min prior to stem cell transplantation. Animals were sacrificed either short term at 2 h or middle term seven days after transplantation. Immunohistochemical techniques to detect alkaline phosphatase activity were used to identify the transplanted cells within the liver parenchyma. Results Anti-CD54 and anti-CD61 administration increases vascular patency and cell engraftment. This represents a 32% and 45% increase, respectively, of engrafted cells compared to the control (p < 0.05). Conclusion Modification of the vascular wall with monoclonal antibodies against endothelial adhesion molecules before cell transplantation enhances cell engraftment into the mouse liver.