Long-term function of islets encapsulated in a redesigned alginate microcapsule construct in omentum pouches of immune-competent diabetic rats.

Long-term function of islets encapsulated in a redesigned alginate microcapsule construct in omentum pouches of immune-competent diabetic rats.
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DOI:
10.1097/mpa.0000000000000107
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发表时间:
2014-05
期刊:
影响因子:
2.9
通讯作者:
Opara EC
Opara EC
中科院分区:
医学4区
文献类型:
--
作者:
Pareta R;McQuilling JP;Sittadjody S;Jenkins R;Bowden S;Orlando G;Farney AC;Brey EM;Opara EC

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我们的研究目的是确定包封的胰岛移植物在网膜袋中的生存能力以及从我们重新设计的藻酸盐微胶囊中释放的FGF-1对移植物功能的影响。将分离的大鼠胰岛包封在由1.5%低粘度高甘露糖醛酸(LVM)藻酸盐制成的内核中,然后在直径测量为300 - 400 μm的微胶囊中由1.25%低粘度高古洛糖醛酸(LVG)藻酸盐(含或不含FGF-1)制成的外层中。两个藻酸盐层通过用0.1%聚-L-鸟氨酸(PLO)制成的选择性渗透膜分离,并使用55 mM柠檬酸钠部分螯合内部LVM核心2 min。在链脲佐菌素糖尿病刘易斯大鼠中,包封胰岛同种异体移植物(约2000个胰岛/kg)的边缘质量导致血糖水平显著降低,与用包封胰岛同种移植物观察到的效果相似。与仅接受同种异体胰岛的受者相比,与FGF-1共包封的同种异体胰岛的移植并没有导致更好的血糖控制,但诱导了移植受者更大的体重维持。取回的组织的组织学检查证明微囊中的胰岛在形态和功能上完整,没有纤维化的迹象。我们的结论是,网膜是一个可行的网站封装胰岛移植。
Our study aim was to determine encapsulated islet graft viability in an omentum pouch and the effect of FGF-1 released from our redesigned alginate microcapsules on the function of the graft. Isolated rat islets were encapsulated in an inner core made with 1.5% low-viscosity high-mannuronic acid (LVM) alginate followed by an external layer made with 1.25% low-viscosity high-guluronic acid (LVG) alginate with or without FGF-1, in microcapsules measuring 300 – 400 μm in diameter. The two alginate layers were separated by a perm-selective membrane made with 0.1 % Poly-L-Ornithine (PLO), and the inner LVM core was partially chelated using 55 mM sodium citrate for 2 min. A marginal mass of encapsulated islet allografts (~2000 islets/kg) in Streptozotocin-diabetic Lewis rats caused significant reduction in blood glucose levels similar to the effect observed with encapsulated islet isografts. Transplantation of allo-islets co-encapsulated with FGF-1 did not result in better glycemic control, but induced greater body weight maintenance in transplant recipients compared to those that received only allo-islets. Histological examination of the retrieved tissue demonstrated morphologically and functionally intact islets in the microcapsules, with no signs of fibrosis. We conclude that the omentum is a viable site for encapsulated islet transplantation.