We have previously shown that
mitomycin C (MMC) treatment of donor tissue resulted in significant prolongation of graft survival in allo- and
xenotransplantation models. However, the mechanisms involved in this prolongation are not clearly understood. This study aims to shed light on the immune responses to MMC-treated islet
xenografting under the kidney
capsule.
Collagenase-digested WS (RT1k) rat islets incubated for 30 min with MMC and subsequently cultured for 20 h were transplanted into the renal subcapsular space of
streptozotocin-induced diabetic C57BL/6 (B6;H-2b) mice. The grafts were harvested on postgrafting day 7 and sections were prepared and stained by
hematoxylin and
eosin (H&E). Histological study of the grafts in a group not treated with MMC showed marked cellular infiltration and destruction of islet clusters, whereas that of MMC-treated grafts demonstrated a
bleb formation under the kidney
capsule, in which islet cell clusters were reorganized, creating a layer of cells fixed to the interior of the
bleb. Minimal invasion by inflammatory cells was observed only at the edge of the
bleb, and most islet cells were protected from these infiltrating cells. In conclusion, MMC treatment induces remodeling of islet structure and forms a
bleb under the kidney
capsule, where no inflammatory cell infiltration occurs, suggesting that this site is a kind of immunologically privileged environment for xenografted islets.