Vascularized tissue engineering mouse chamber model supports thymopoiesis of ectopic thymus tissue grafts

We have previously established a chamber model of tissue engineering that promotes de novo angiogenesis and vascularization of engrafted cells and tissues when combined with an extracellular matrix. Here we demonstrate that the mouse chamber (MC) model can sustain ectopic grafts of murine fetal thymus lobes and, to a limited degree, human pediatric thymus tissue, resulting in de novo T-cell production. Silicone chambers containing Matrigel((R)) and thymus tissues were placed around exposed epigastric vessels and the ends sealed with bone wax, before implantation into the inguinal fat pad of athymic Balb/c(nu/nu) (nude) mice. Murine, embryonic day 15 (E15) thymus grafts were found to be well vascularized and viable within the MC upon harvest at week 11. In contrast, engraftment of both adult murine and pediatric human thymus tissue was limited, with only one out of the seven human thymus grafts sustaining mature, murine-derived T-cell development. Increased CD4(+) and CD8(+) T-cell numbers were observed in the peripheral blood of nude mice within 2 weeks after E15 thymus-MC grafts (n = 8), compared with nude control mice. Peripheral blood T-cell percentage and subset distribution were comparable to mice receiving conventional thymus kidney capsule grafts. T-cell function of both kidney capsule- and MC-E15 thymus grafts was established via successful rejection of major histocompatibility complex (MHC)-mismatched skin grafts. Sustained growth of fetal thymus tissue in the MC provides an alternative model for the study of thymopoiesis and related applications of T-cell-mediated immunity.