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

Natalie Louise Seach, Monika Mattesich, Keren Abberton, Ken Matsuda, Daniel J Tilkorn, John Rophael, Richard Lennox Boyd, Wayne A Morrison

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    Abstract

    We have previously established a chamber model of tissue engineering which promotes de novo angiogenesis and vascularization of engrafted cells and tissue when combined with an extracellular matrix. Here we demonstrate 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 tissue were placed around exposed epigastric vessels and the ends sealed with bone wax, before implantation into the inguinal fat pad of athymic Balb/cnu/nu (nude) mice. Murine, embryonic day 15 (E15) thymus grafts were found to be well-vascularized and viable within the mouse chamber upon harvest at week 11. In contrast, engraftment of both adult murine and peadiatric human thymus tissue was limited, with only one out of seven human thymus grafts sustaining mature, murine-derived T cell development. Increased CD4+ and CD8+ T cell numbers were observed in the peripheral blood (PB) of nude mice within two weeks post E15 thymus- MC grafts (n=8), compared to nude control mice. PB T cell percentage and subset distribution were comparable to mice receiving conventional thymus kidney capsule (KC) grafts. T cell function of both KC- and MC- E15 thymus grafts was established via successful rejection of 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.
    Original languageEnglish
    Pages (from-to)543 - 551
    Number of pages8
    JournalTissue Engineering Part C: Methods
    Volume16
    DOIs
    Publication statusPublished - 2010

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