In vivo selection of biocompatible alginates for islet encapsulation and subcutaneous transplantation.
In vivo selection of biocompatible alginates for islet encapsulation and subcutaneous transplantation.
复制标题
用于胰岛封装和皮下移植的生物相容性藻酸盐的体内选择。
DOI：
10.1089/ten.tea.2009.0286
复制
发表时间：
2010
影响因子：
--
通讯作者：
D. Dufrane
中科院分区：
文献类型：
--
作者：
S. Vériter;Julien Mergen;R. Goebbels;Najima Aouassar;Charles Grégoire;B. Jordan;P. Lévêque;B. Gallez;P. Gianello;D. Dufrane
胰岛包裹需要几种性质，包括(1)生物相容性，(2)免疫保护，(3)为胰岛存活和纠正糖尿病而扩散的氧气。对新型化学海藻酸盐进行了体内实验，并与传统的高甘露酸海藻酸盐和古鲁酸盐海藻酸盐进行了比较。为了改善细胞在基质中的粘附性，将具有偶联多肽序列的新型海藻酸盐(无菌冻干高甘露糖酸盐[SLM]-RGD3%和无菌冻干高甘露糖酸[SLG]-RGD3%)和极低粘度(VLDM7%和VLDG7%)的海藻酸盐(VLDM7%和VLDG7%)植入70只Wistar大鼠的皮下，以比较高粘度和高甘露醛酸含量(SLM3%)或古龙酸(SLG3%)的海藻酸盐。在植入前、植入后2周、4周和12周，对藻酸盐对36 kDa、75 kDa和150 kDa与异硫氰酸荧光素偶联的凝集素的渗透性进行了量化。在每个移植时间评估生物相容性(纤维化、移植物稳定性、CD3/CD68细胞的免疫浸润和新生血管)。发现所有海藻酸盐对小分子都有渗透性。植入前只有3%的人观察到对150 kDa分子，如免疫球蛋白G的不通透性，并在植入后保持到12周。与其他藻酸盐相比，SLM3%和SLG3%表现出更好的移植物稳定性，CD3/CD68募集和纤维化程度更低。体内电子顺磁共振血氧测定仪显示，SLM3%可显著促进血管生成，并在植入后4周内将氧压维持在约40 mm Hg。SLM包裹的猪胰岛植入大鼠皮下，无炎症/免疫反应，胰岛功能可达60天而不受免疫抑制。由高甘露醇含量(SLM3%)制成的传统藻酸盐是一种适合于皮下组织中胰岛免疫保护的材料。较低的粘度和使用GRGDSP-多肽序列没有发现改善。
Islet encapsulation requires several properties including (1) biocompatibility, (2) immunoprotection, and (3) oxygen diffusion for islet survival and diabetes correction. New chemical alginates were tested in vivo and compared with traditional high-mannuronate and -guluronate alginates. New alginates with coupled peptide sequence (sterile lyophilized high mannuronate [SLM]-RGD3% and sterile lyophilized high guluronate [SLG]-RGD3%), to improve encapsulated cell adherence in the matrix, and alginates with a very low viscosity (VLDM7% and VLDG7%), to reduce implant size by loading a higher number of islets per volume of polymer, were implanted subcutaneously in 70 Wistar rats for comparison with alginates of high viscosity and high content of mannuronic (SLM3%) or guluronic acids (SLG3%). Permeability of alginates to 36-, 75-, and 150-kDa lectins coupled to fluorescein isothiocynate was quantified before implantation and at 2, 4, and 12 weeks after implantation. Biocompatibility (fibrosis, graft stability, immunologic infiltration by CD3/CD68 cells, and neovascularization) was assessed at each explantation time. Permeability to small molecules was found for all alginates. Impermeability to 150-kDa molecules, such as IgG, was observed only for SLM3% before implantation and was maintained up to 12 weeks after implantation. SLM3% and SLG3% demonstrated better graft stability with lower CD3/CD68 recruitment and fibrosis than the other alginates. SLM3% induced a significantly higher angiogenesis and maintained oxygen pressure at approximately 40 mm Hg for up to 4 weeks after implantation as measured by in vivo electronic paramagnetic resonance oximetry. SLM-encapsulated pig islets implanted subcutaneously in rats demonstrated no inflammatory/immunologic reactions and islets functioned for up to 60 days without immunosuppression. A traditional alginate made of high mannuronic content (SLM3%) is an adapted material to immunoprotect islets in subcutaneous tissue. No improvement was found with lower viscosity and use of GRGDSP-peptide sequence.
影响因子：
14
作者：
Evangelista, Marta B.;Hsiong, Susan X.;Granja, Pedro L.
通讯作者：
Granja, Pedro L.
影响因子：
14
作者：
Burdick, JA;Anseth, KS
通讯作者：
Anseth, KS