Rafael E, Wu G S, Hultenby K, Tibell A, Wernerson A
Department of Transplantation Surgery, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden.
Cell Transplant. 2003;12(4):407-12. doi: 10.3727/000000003108746957.
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 beta-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.
将细胞包裹在半透膜中，未来可能为治疗多种内分泌和神经疾病提供机会，而无需终身免疫抑制。该装置中的生理条件是移植物存活的关键因素。此前，我们已经表明，植入后约3个月，免疫隔离膜两侧的物质交换以及TheraCyte装置周围的微循环会增加。本研究的目的是确定预先植入TheraCyte装置是否会提高随后移植的胰岛移植物的存活率。将一个TheraCyte装置皮下植入非糖尿病SD大鼠背部一侧。3个月后，将从SD大鼠分离的1500个胰岛通过装置端口进行移植。同时，在背部另一侧植入另一个装有相同数量胰岛的装置。胰岛移植2周后（即分别在装置植入后3.5个月和0.5个月）将两个装置取出。通过形态计量学评估6对装置。预先植入装置中存活胰岛的体积密度为0.22±0.04，而未预先植入的装置中为0.06±0.03（p<0.05）。纤维化和坏死的相应体积密度分别为0.64±0.13和0.85±0.08（p<0.05），以及0.11±0.14和0.09±0.07（无显著差异）。当计算绝对体积（mm³）时，预先植入装置中含有1.1±0.7个内分泌细胞，而未预先植入的装置中含有0.4±0.2个（p<0.05）。预先植入与未预先植入装置中胰岛素阳性β细胞的百分比分别为80±5%和67±6%（p<0.01）。纤维化组织的相应体积为3.0±1.8和5.2±1.2（p<0.05），而坏死组织的量无显著差异（0.42±0.5和0.50±0.3）。预先植入TheraCyte装置似乎可提高包裹胰岛移植物的存活率，并减少装置中成纤维细胞的生长。
