Laboratory of Experimental Surgery, Université Catholique de Louvain, Faculté de Médecine, Brussels, Belgium.
Tissue Eng Part A. 2010 May;16(5):1503-13. doi: 10.1089/ten.TEA.2009.0286.
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.
（1）生物相容性，（2）免疫保护，以及（3）氧气扩散，以确保胰岛细胞的存活和糖尿病的纠正。新型化学海藻酸盐在体内进行了测试，并与传统的高甘露糖醛酸和高古洛糖醛酸海藻酸盐进行了比较。具有偶联肽序列的新型海藻酸盐（无菌冻干高甘露糖醛酸[SLM]-RGD3%和无菌冻干高古洛糖醛酸[SLG]-RGD3%），以改善包封细胞在基质中的黏附性，以及具有非常低黏度的海藻酸盐（VLDM7%和 VLDG7%），通过在聚合物体积内装载更多数量的胰岛细胞来减小植入物的大小，被植入 70 只 Wistar 大鼠的皮下组织中，与高黏度和高甘露糖醛酸（SLM3%）或古洛糖醛酸（SLG3%）含量的海藻酸盐进行比较。在植入前和植入后 2、4 和 12 周，用荧光素异硫氰酸酯偶联的 36、75 和 150 kDa 凝集素定量测定海藻酸盐的通透性。在每次取出时评估生物相容性（纤维化、移植物稳定性、CD3/CD68 细胞的免疫浸润和新生血管形成）。所有海藻酸盐均具有小分子的通透性。只有在植入前，SLM3%对 150 kDa 分子（如 IgG）才表现出不可渗透性，这种状态一直持续到植入后 12 周。与其他海藻酸盐相比，SLM3%和 SLG3%的移植物稳定性更好，CD3/CD68 募集和纤维化程度更低。SLM3% 诱导的血管生成明显更高，并通过体内电子顺磁共振血氧定量法测量，在植入后 4 周内将氧压维持在约 40 mmHg。植入大鼠皮下组织的 SLM 包封的猪胰岛细胞未引起炎症/免疫反应，并且在没有免疫抑制的情况下功能可维持长达 60 天。由高甘露糖醛酸含量（SLM3%）组成的传统海藻酸盐是一种适应于在皮下组织中免疫保护胰岛的材料。降低黏度和使用 GRGDSP 肽序列没有发现任何改善。
