Lanza R P, Butler D H, Borland K M, Staruk J E, Faustman D L, Solomon B A, Muller T E, Rupp R G, Maki T, Monaco A P
BioHybrid Technologies, Inc., Shrewsbury, MA 01545.
Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11100-4. doi: 10.1073/pnas.88.24.11100.
Permselective acrylic membranes were employed to prevent immune rejection of discordant islet xenografts isolated from various large animals. Canine, porcine, and bovine islets were seeded into tubular diffusion chambers and transplanted into the peritoneum of 27 nonimmunosuppressed streptozotocin-induced diabetic Lewis rats. Six recipients received islet grafts from bovine calves, 7 received grafts from pigs, and 14 received grafts from dogs. Four of the latter were removed at 1 month. In the control group of 10 diabetic rats, 4 received nonencapsulated canine islets, 3 received nonencapsulated bovine islets, and 3 received nonencapsulated porcine islets. Recipients of encapsulated islets promptly dropped from a pretransplantation plasma glucose level of 487 +/- 36 (mean +/- SEM) to 84 +/- 2 (canine), 81 +/- 4 (bovine), and 81 +/- 3 mg/dl (porcine) during the first week. All of the animals sustained these levels for at least 1 month. One rat spontaneously reverted to diabetes at 54 days posttransplantation; 4 other rats became hyperglycemic (glucose, greater than 600 mg/dl) after membrane removal on day 30. The remaining 22 rats maintained fasting euglycemia for greater than 10 weeks. In contrast, rats that received nonencapsulated islets became hyperglycemic in less than 7 days. Intravenous glucose tolerance test K values (decline in glucose levels, %/min) at 1 month for the canine and bovine encapsulated islet transplant group were 3.5 +/- 0.3 and 3.3 +/- 0.1 compared with 3.3 +/- 0.1 (P = 0.63) and 0.91 +/- 0.1 (P less than 0.0001) for normal (n = 4) and diabetic (n = 4) control groups. Morphologic studies of long-term functioning grafts (30-130 days) revealed well-preserved alpha, beta, and delta cells, with varying degrees of granulation. These results demonstrate that immune isolation of islet tissue using permselective artificial membranes can protect discordant islet xenografts from immune rejection in the absence of any immunosuppressive drugs.
采用具有渗透选择性的丙烯酸膜来防止从各种大型动物分离的异种胰岛移植发生免疫排斥。将犬、猪和牛的胰岛接种到管状扩散室中，并移植到27只未接受免疫抑制的链脲佐菌素诱导的糖尿病Lewis大鼠的腹膜内。6只受体接受来自小牛的胰岛移植，7只接受来自猪的胰岛移植，14只接受来自犬的胰岛移植。其中4只在1个月时被移除。在10只糖尿病大鼠的对照组中，4只接受未封装的犬胰岛，3只接受未封装的牛胰岛，3只接受未封装的猪胰岛。接受封装胰岛的受体在移植后的第一周内，血浆葡萄糖水平迅速从移植前的487±36（平均值±标准误）降至84±2（犬）、81±4（牛）和81±3mg/dl（猪）。所有动物维持这些水平至少1个月。1只大鼠在移植后54天自发恢复糖尿病；另外4只大鼠在第30天移除膜后血糖升高（血糖大于600mg/dl）。其余22只大鼠维持空腹血糖正常超过10周。相比之下，接受未封装胰岛的大鼠在不到7天内血糖升高。犬和牛封装胰岛移植组在1个月时的静脉葡萄糖耐量试验K值（血糖水平下降百分比/分钟）分别为3.5±0.3和3.3±0.1，而正常（n = 4）和糖尿病（n = 4）对照组分别为3.3±0.1（P = 0.63）和0.91±0.1（P < 0.0001）。对长期功能良好的移植（30 - 130天）进行形态学研究发现，α、β和δ细胞保存良好，颗粒化程度不同。这些结果表明，在没有任何免疫抑制药物的情况下，使用具有渗透选择性的人工膜对胰岛组织进行免疫隔离可以保护异种胰岛移植免受免疫排斥。
