Maintaining functional islets through encapsulation in an injectable saccharide-peptide hydrogel.
Maintaining functional islets through encapsulation in an injectable saccharide-peptide hydrogel.
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DOI：
10.1016/j.biomaterials.2013.02.007
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发表时间：
2013-05
期刊：
影响因子：
14
通讯作者：
Mullen, Yoko
中科院分区：
文献类型：
--
作者：
Liao, Sophia W.;Rawson, Jeffrey;Omori, Keiko;Ishiyama, Kohei;Mozhdehi, Davoud;Oancea, Alina R.;Ito, Taihei;Guan, Zhibin;Mullen, Yoko
胰岛移植为 1 型糖尿病 (T1D) 提供了一种有前景的治疗方法。然而，这种治疗的一个主要障碍是在培养过程中和移植后功能性胰岛的快速丧失。目前用于移植的肝脏部位对于实现长期胰岛素独立而言不是最佳的，因为移植后胰岛功能迅速丧失，随后又慢性下降。在此，我们报道了一种合成的糖肽（SP）水凝胶，它允许将胰岛悬浮在液体中并注射进行原位聚合而不形成胰岛团块，表明其在肝外胰岛移植中的潜力。在体外，SP 水凝胶中的大鼠胰岛在 4 周内保持了与新鲜分离的胰岛中观察到的相似的 3D 结构和高葡萄糖刺激的胰岛素释放，而悬浮培养的对照胰岛在 2 周内失去了其 3D 结构和胰岛素释放反应。 SP水凝胶的生物相容性通过体外暴露于水凝胶的外周血单核细胞(PBMC)中不存在细胞因子mRNA激活以及皮下植入的水凝胶内部和周围不存在细胞浸润来证明。移植到不同肝外位点的 SP 水凝胶中的同源 Lewis 大鼠胰岛对胰岛素染色强烈，并且当移植到网膜袋中时比未封装的胰岛更有效地逆转糖尿病。总之，SP 水凝胶是非细胞毒性的，并且在体外和体内支持正常的胰岛结构和功能。具体而言，水凝胶在移植后分离单个胰岛的能力对于维持其体内功能非常重要。这一重要特性与多功能性和生物相容性相结合，使我们的 SP 水凝胶成为一种有前途的合成支架，可以促进有组织的异质细胞的移植，以保留其微观结构和功能。
Islet transplantation offers a promising treatment for type 1 diabetes (T1D). However, a major hurdle in this treatment is the rapid loss of functional islets during culture and after transplantation. The liver site, currently utilized for transplantation, is suboptimal for achieving long-term insulin independence due to a rapid islet loss followed by a chronic decline in islet function after transplantation. Herein, we report a synthetic saccharide-peptide (SP) hydrogel that allows suspending islets in liquid and injecting for in situ polymerization without forming islet clumps, indicating its potential in extrahepatic islet transplantation. In vitro, rat islets in SP hydrogel maintained a 3D structure and high glucose-stimulated insulin release similar to that observed in freshly isolated islets for 4 weeks, while control islets cultured in suspension lost their 3D structure and insulin release responses by 2 weeks. Biocompatibility of SP hydrogel was shown by the absence of cytokine mRNA activation in peripheral blood mononuclear cells (PBMC) exposed to hydrogel in vitro and by the absence of cellular infiltrates in and around the hydrogel implanted subcutaneously. Syngeneic Lewis rat islets transplanted in SP hydrogel in various extrahepatic sites stained strongly for insulin, and more effectively reversed diabetes than unencapsulated islets when transplanted in an omental pocket. In conclusion, the SP hydrogel is non-cytotoxic and supports normal islet structure and function both in vitro and in vivo. Specifically, the ability of the hydrogel to separate individual islets after transplantation is important for maintaining their function in vivo. This important property, combined with the versatility and biocompatibility, makes our SP hydrogel a promising synthetic scaffold that can facilitate transplantation of organized heterogeneous cells to preserve their micro-structure and function.
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影响因子：
6.2
作者：
Lin, Chien-Chi;Anseth, Kristi S.
通讯作者：
Anseth, Kristi S.
影响因子：
6.2
作者：
Blomeier, Herman;Zhang, Xiaomin;Lowe, William L., Jr.
通讯作者：
Lowe, William L., Jr.
影响因子：
6.2
作者：
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Guan, Zhibin
影响因子：
6.2
作者：
Hakamata, Y;Murakami, T;Kobayashi, E
通讯作者：
Kobayashi, E
影响因子：
3.3
作者：
Stendahl JC;Kaufman DB;Stupp SI
通讯作者：
Stupp SI