Sörenby Anne K, Kumagai-Braesch Makiko, Sharma Amit, Hultenby Kjell R, Wernerson Annika M, Tibell Annika B
Division of Transplantation Surgery, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
Transplantation. 2008 Jul 27;86(2):364-6. doi: 10.1097/TP.0b013e31817efc78.
Islet graft survival inside macroencapsulation devices is suboptimal. We hypothesized that induction of neovascularization by preimplantation of devices would improve the physiological conditions, thereby lowering the number of islets required for cure. Several rat islets were transplanted to TheraCyte immunoprotective devices implanted subcutaneously in diabetic athymic mice. Cure rates in the groups with preimplanted devices were significantly better than in those with freshly implanted devices (375 islets: 8/8 vs. 1/6, P=0.003; 125 islets: 6/6 vs. 0/7, P=0.001). Morphometric evaluations of the 125 islet groups showed higher fractional and absolute volumes of endocrine tissue in the group with preimplanted devices (P<0.001 and P=0.035, respectively). In the following dose titration study, using preimplanted devices, as low as 50 islets cured diabetic mice (100% cure, n=6). We conclude that preimplantation significantly lowers the curative dose of macroencapsulated islets to levels resembling those of free islets transplanted under the renal capsule.
胰岛在大封装装置内的存活情况并不理想。我们假设通过预先植入装置诱导血管生成会改善生理状况，从而降低治愈所需的胰岛数量。将若干大鼠胰岛移植到植入糖尿病无胸腺小鼠皮下的TheraCyte免疫保护装置中。预先植入装置组的治愈率显著高于新鲜植入装置组（375个胰岛：8/8对1/6，P = 0.003；125个胰岛：6/6对0/7，P = 0.001）。对125个胰岛组的形态计量学评估显示，预先植入装置组的内分泌组织分数体积和绝对体积更高（分别为P < 0.001和P = 0.035）。在接下来的剂量滴定研究中，使用预先植入的装置，低至50个胰岛就能治愈糖尿病小鼠（治愈率100%，n = 6）。我们得出结论，预先植入能显著降低大封装胰岛的治愈剂量，使其达到与肾被膜下移植的游离胰岛相似的水平。
