Recruitment of mononuclear leucocytes to osteoarthritic human synovial xenografts in the ears of SCID mice

A system has been established to assess the recruitment of Tc-99m-hexamethy lpropylene amine oxamine (Tc-99m-HMPAO)-labelled PBMC and [I-125]iododeoxyu ridine-labelled Con A stimulated lymphoblasts to allogeneic human synovial xenografts in the ears of SCID mice. Successful engraftment of osteoarthrit ic synovium was achieved in approximately 90% of cases and a connection bet ween the human microvasculature of the xenograft and the circulation of the mouse was shown. Cells were delivered to the xenograft by a system of regi onal vascular perfusion, thus avoiding the major murine vascular beds. The accumulation of Tc-99m-HMPAO-labelled PBMC in mouse ears was monitored in r eal time. Direct injection of xenograft-bearing ears with recombinant human TNF-alpha, 7 h prior to perfusion, increased the accumulation of both PBMC and lymphoblasts in cytokine-injected ears compared to contralateral contr ol-injected ears. Autoradiography revealed the presence of [I-125]iododeoxy uridine-labelled lymphoblasts associated with human microvasculature within the xenograft. However, the increased accumulation of lymphoblasts in cyto kine-injected ears occurred in the tissues surrounding the xenograft, where lymphoblasts were associated more often with murine than human vessels. Al though the system described offers advantages over similar models, the prop ensity for mouse endothelium to interact with human leucocytes is likely to be a generic disadvantage for models of human leucocyte recruitment to xen ografts in immunodeficient mice.