Long-term normoglycemia in rats receiving transplants with encapsulated islets
Long-term normoglycemia in rats receiving transplants with encapsulated islets
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DOI：
10.1097/01.tp.0000149340.37865.46
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发表时间：
2005-01-15
期刊：
影响因子：
6.2
通讯作者：
Weir, GC
中科院分区：
文献类型：
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作者：
Omer, A;Duvivier-Kali, V;Weir, GC
背景。本研究以大鼠为实验对象，研究海藻酸盐组成、交联剂浓度、胶囊大小等因素对包封胰岛效果的影响。采用高古鲁醛酸或高甘露醛酸的高纯度海藻酸盐，内毒素含量低。通过与BaCl2交联制备常规大小（0.8-1.1 mm）或小微胶囊（0.5-0.7 mm），无需额外包被聚l -赖氨酸，并将其移植到血糖正常（空胶囊）或链脲霉素诱导的糖尿病Lewis大鼠腹腔（含胰岛胶囊）。不同海藻酸盐组成的空胶囊具有相似的生物相容性和稳定性。与空胶囊相比，含有同基因胰岛的高m海藻酸盐制成的常规尺寸胶囊的稳定性较差，回收体积分数较低。同种异体实验中，接受小尺寸微胶囊移植的大鼠（48 +/- 8天，n = 8）和接受小尺寸微胶囊移植的大鼠（59 +/- 11天，n = 4）的正常血糖周期相似，但含有胰岛的小尺寸海藻酸盐微胶囊比常规尺寸微胶囊更稳定，细胞附着更少。在同基因实验中，所有大鼠（n = 4）在移植后210天内血糖均保持正常。这些结果表明，常规大小的海藻酸盐胶囊在大鼠身上的效果不如我们之前在小鼠身上的实验好。由海藻酸盐与钡交联制成的小胶囊似乎具有更好的稳定性，并且可能是用于较大受体的有用策略。
Background. To follow up on previously successful transplantation of encapsulated islets in mice, the present study was performed in rats to determine the effects of several factors, including alginate composition and concentration of cross-linking agent and capsule size on the effectiveness of encapsulated islets.Methods. Highly purified alginate of either high guluronic acid or high mannuronic acid (M) with low endotoxin content was used. Regular-size (0.8-1.1 mm) or small microcapsules (0.5-0.7 mm) were produced by cross-linking with BaCl2 without additional poly-L-lysine coating and were transplanted into abdominal cavity of normoglycemic (empty capsules) or streptozotocin induced diabetic Lewis rats (islet containing capsules).Results. Empty regular-size capsules made of different alginate compositions had similar biocompatibility and stability results. Compared with empty capsules, regular-size capsules made of high-M alginate containing syngeneic islets had inferior stability indicated with lower fractional volume retrieved. Islet-containing smaller-size microcapsules made of high-M alginate were more stable and had less cellular attachment compared with the regular-size capsules, although the normoglycemic period was comparable between two groups of rats receiving transplants with smaller-size microcapsules (48 +/- 8 days, n = 8) or regular-size capsules (59 +/- 11 days, n = 4) in allogeneic experiments. In syngeneic experiments, all of the rats (n = 4) maintained normoglycemia up to 210 days after transplantation.Conclusion. These results indicate that regular-size alginate capsules do less well in rats than in our previous experiments with mice. Smaller capsules made of alginate cross-linked with barium appear to provide better stability and may be a useful strategy for use in larger recipients.