Review: Macro-Encapsulation of Islets in Polyvinyl Alcohol Hydrogel
Review: Macro-Encapsulation of Islets in Polyvinyl Alcohol Hydrogel
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DOI：
10.5405/jmbe.1579
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发表时间：
2014-06
影响因子：
2
通讯作者：
S. Sumi;G. Yanai;M. Qi;N. Sakata;Zhi Qi;Kai-Chiang Yang;Y. Shirouzu;A. Hiura;Y. Gu;
中科院分区：
文献类型：
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作者：
S. Sumi;G. Yanai;M. Qi;N. Sakata;Zhi Qi;Kai-Chiang Yang;Y. Shirouzu;A. Hiura;Y. Gu;
糖尿病（DM）可以通过从相对较小体积的细胞中分泌足够的胰岛素来治愈。细胞包封使得同种异体甚至异种细胞治疗成为可能，而无需免疫抑制。在最近的临床试验中使用的微囊化胰岛在移植后不能完全回收。本文综述了利用聚乙烯醇（PVA）水凝胶制备可回收和理论上可置换的大囊化胰岛的研究进展。PVA的水溶液通过冷冻和解冻通过微结晶变成凝胶。利用这一特征，开发了PVA-宏包封的胰岛（PVA-MEI）。将悬浮在含有3%PVA的Euro-Collins溶液中的大鼠胰岛通过冷冻和解冻包封在网状增强的PVA水凝胶片中。在体外和体内测试了PVA-MEIs用于DM治疗的可行性。PVA-MEIs在体外显示葡萄糖响应性胰岛素分泌，即使在14天的培养后。在含有新鲜人血浆的培养基中培养的大鼠PVA-MEIs没有显示出形态学变化，并保持胰岛素含量。腹腔内移植含有750个大鼠胰岛的PVA-MEIs可将链脲佐菌素（STZ）诱导的糖尿病小鼠的高血糖症改善至接近正常水平长达30天，体重持续增加。PVA-MEIs的移植也预防了STZ诱导的糖尿病小鼠的代谢和肾脏疾病。PVA-MEIs冷冻保存1，7和30天显示出相似的功能，在体外和纠正STZ诱导的糖尿病小鼠腹腔内移植后的高血糖。含有同种或同种异体胰岛的PVA-MEI的腹膜内移植（约2，000个胰岛）以类似的方式改善STZ诱导的糖尿病大鼠的高血糖，持续几乎半年，尽管功效随着时间逐渐降低。PVA-MEIs移植可改善无免疫抑制的糖尿病小鼠和大鼠的高血糖。可回收的和理论上可替换的PVA-MEI可以确保细胞截留，可以减轻与异种细胞和由未分化细胞制成的细胞相关的潜在风险。因此，PVA-MEIs是未来DM治疗的一种有前途的方式。
Diabetes mellitus (DM) can be cured by adequate insulin secretion from a relatively small volume of cells. Cell encapsulation enables allo- and even xeno-geneic cell therapy without immunosuppression. Micro-encapsulated islets used in recent clinical trials are not fully retrievable after transplantation. This paper summerizes the development of retrievable and theoretically replaceable macro-encapsulated islets using polyvinyl alcohol (PVA) hydrogel. An aqueous solution of PVA becomes a gel through micro crystallization by freezing and thawing. Utilizing this feature, PVA-macro-encapsulated islets (PVA-MEIs) were developed. Rat islets suspended in Euro-Collins solution containing 3% PVA were encapsulated in a mesh-reinforced PV A hydrogel sheet by freezing and thawing. The feasibility of PVA-MEIs for DM therapy was tested in vitro and in vivo. PVA-MEIs showed glucose-responsive insulin secretion in vitro even after 14-day culture. Rat PVA-MEIs cultured in media containing fresh human plasma showed no morphological changes and maintained insulin content. Intra-peritoneal transplantation of PVA-MEIs containing 750 rat islets ameliorated hyperglycemia in streptozotocin (STZ)-induced diabetic mice to nearly normal levels for up to 30 days with a consistent increase in body weight. Transplantation of PVA-MEIs also prevented metabolic and renal disorders in STZ-induced diabetic mice. PVA-MEIs cryo-preserved for 1, 7, and 30 days showed similar function in vitro and corrected hyperglycemia after intra-peritoneal transplantation in STZ-induced diabetic mice. Intra-peritoneal transplantation of PVA-MEIs containing iso- or allo-geneic islets (approx. 2,000 islets) ameliorated hyperglycemia in STZ-induced diabetic rats in a similar manner for almost half a year although the efficacy gradually decreased with time. Transplantation of PVA-MEIs ameliorated hyperglycemia in diabetic mice and rats without immunosupression. Retrievable and theoretically replaceable PVA-MEIs that can secure cell entrapment can mitigate the potential risks associated with xeno-geneic cells and cells made from undifferentiated cells. Therefore, PVA-MEIs are a promising modality for future DM therapy.