Improved Survival of Macroencapsulated Islets of Langerhans by Preimplantation of the Immunoisolating Device: A Morphometric Study

Abstract

Encapsulation of cells in a semipermeable membrane may in the future provide an opportunity to treat a variety of endocrine and neurological disorders, without the need for lifelong immunosuppression. The physiological conditions in the device are crucial factors for graft survival. Previously, we have shown that the exchange across the immunoisolating membrane and the microcirculation around the TheraCyte™ device increase around 3 months after implantation. The aim of this study was to determine whether preimplantation of the TheraCyte™ device would improve the survival of a later transplanted islet graft. A TheraCyte™ device was implanted SC on one side of the back of a nondiabetic SD rat. After 3 months, 1500 islets isolated from SD rats were transplanted via the device port. At the same time, another device, loaded with the same number of islets, was implanted on the other side of the back. Both devices were explanted 2 weeks after islet transplantation (i.e., 3.5 months and 0.5 month after device implantation, respectively). Six pairs of devices were evaluated by morphometery. The volume densities of viable islets were 0.22 ± 0.04 in the preimplanted device vs. 0.06 ± 0.03 in the nonpreimplanted one (p < 0.05). The corresponding volume densities of fibrosis and necrosis were 0.64 ± 0.13 vs. 0.85 ± 0.08 (p < 0.05) and 0.11 ± 0.14 vs. 0.09 ± 0.07 (ns), respectively. When the absolute volumes (mm3) were calculated, preimplanted devices contained 1.1 ± 0.7 endocrine cells while nonpreimplanted ones contained 0.4 ± 0.2 (p < 0.05). The percentages of insulin-positive β-cells in the preimplanted versus nonpreimplanted device were 80 ± 5% and 67 ± 6%, respectively (p < 0.01). The corresponding volumes of fibrotic tissue were 3.0 ±1.8 vs. 5.2 ± 1.2 (p < 0.05), while the amount of necrotic tissue did not differ significantly (0.42 ± 0.5 vs. 0.50 ± 0.3). Preimplantation of the TheraCyte™ device seems to improve the survival of an encapsulated islet graft and reduce fibroblast outgrowth in the device.