Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, Brazil.
Núcleo de Terapia Celular e Molecular (NUCEL), Departamento de Clínica Médica, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
J Tissue Eng Regen Med. 2019 Oct;13(10):1912-1922. doi: 10.1002/term.2942. Epub 2019 Aug 6.
Cell encapsulation coats cells with an artificial membrane to preserve their physical and functional integrity. Different approaches try to develop more functional and biocompatible materials to avoid cell loss after transplantation due to inflammatory reaction, one of the main causes for graft failure. In this study, the LN-Biodritin biomaterial, based on alginate, chondroitin sulfate, and laminin, previously developed by our group, was further improved by replacing laminin by polylaminin, an artificial laminin polymer with anti-inflammatory properties, generating the new biomaterial polyLN-Biodritin. Capsules containing polylaminin are stable, do not induce macrophage activation in vitro, and are also able to prevent macrophage activation by encapsulated human pancreatic islets in vitro, preserving their glucose-stimulated insulin secretion potential. In addition, when empty capsules containing polylaminin were implanted into immunocompetent mice, the inflammatory response towards the implant was attenuated, when compared with capsules without polylaminin. The results indicate that polylaminin incorporation leads to lower levels of pericapsular growth on the capsules surface, lower infiltration of cells into the peritoneal cavity, and lower production of proinflammatory cytokines, both at the implant site (interleukin-12p70 (IL-12p70), tumor necrosis factor-α (TNF-α), monocyte chemotactic protein-1 (MCP-1), and interferon-γ (IFN-γ)) and systemically (IL-12p70 and TNF-α). Therefore, polylaminin incorporation into the microcapsules polymer attenuates the host posttransplantation immune response against implanted microcapsules, being likely to favor maintenance of engrafted encapsulated cells.
细胞包封用人工膜包裹细胞以保持其物理和功能完整性。不同的方法试图开发更具功能性和生物相容性的材料,以避免因炎症反应导致移植后细胞丢失,这是移植物失功的主要原因之一。在这项研究中,我们小组先前开发的基于藻酸盐、硫酸软骨素和层粘连蛋白的 LN-Biodritin 生物材料通过用具有抗炎特性的人工层粘连蛋白聚合物聚层粘连蛋白替代层粘连蛋白进一步得到了改进,生成了新的生物材料聚 LN-Biodritin。含有聚层粘连蛋白的胶囊稳定,不会在体外激活巨噬细胞,并且还能够防止包封的人胰岛在体外激活巨噬细胞,从而保持其葡萄糖刺激的胰岛素分泌潜力。此外,当将含有聚层粘连蛋白的空胶囊植入免疫功能正常的小鼠体内时,与不含聚层粘连蛋白的胶囊相比,植入物的炎症反应得到了减弱。结果表明,聚层粘连蛋白的掺入导致胶囊表面的囊周生长水平降低,细胞渗透到腹腔的程度降低,以及促炎细胞因子的产生减少,无论是在植入部位(白细胞介素 12p70(IL-12p70)、肿瘤坏死因子-α(TNF-α)、单核细胞趋化蛋白-1(MCP-1)和干扰素-γ(IFN-γ))还是全身(IL-12p70 和 TNF-α)。因此,聚层粘连蛋白掺入微胶囊聚合物可减弱宿主对植入微胶囊的移植后免疫反应,可能有利于维持移植的包封细胞。