Accessible xenografts of human synovium in the subcutaneous tissues of the ears of SCID mice

Abstract

This work was undertaken to examine whether human synovium could be engrafted into subcutaneous pouches in the ears of severe combined immunodeficient (SCID) mice. Synovium was transplanted into surgically constructed ear pouches. The grafts were examined by histological and immunohistochemical methods after varying periods after engraftment, or after percutaneous injection of TNF-alpha. Normal, osteo-arthritic and rheumatoid synovium was engrafted successfully in subcutaneous ear pouches. The general morphology and cellular compositions of xenografts were retained including human endothelial cells. In rheumatoid xenografts, macrophages, fibroblasts and lymphocytes persisted for at least 4 weeks. Vascular expression of intercellular adhesion molecule-1 (ICAM-1) was maintained but expression of vascular adhesion molecule-1 (VCAM-1), E-selectin and MHC class II diminished with time. Percutaneous injection of TNF-alpha induced up-regulation of VCAM-1. Human synovium can be engrafted into subcutaneous ear pouches in SCID mice. The xenografts are accessible and respond to injection of a pro-inflammatory cytokine.