de Bont Denise F A, Mohammed Sami G, de Vries Rick H W, Paulino da Silva Filho Omar, Vaithilingam Vijayaganapathy, Jetten Marlon J, Engelse Marten A, de Koning Eelco J P, van Apeldoorn Aart A
Cell Biology-Inspired Tissue Engineering (cBITE), MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, Maastricht, The Netherlands.
Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands.
PLoS One. 2025 Mar 12;20(3):e0298114. doi: 10.1371/journal.pone.0298114. eCollection 2025.
Type 1 diabetic (T1D) patients are life-long dependent on insulin therapy to keep their blood glucose levels under control. An alternative cell-based therapy for exogenous insulin injections is clinical islet transplantation (CIT). Currently the widespread application of CIT is limited, due to risks associated with the life-long use of immunosuppressive drugs to prevent rejection of donor cells. An immunoprotective macroencapsulation device can protect allogeneic islet cells against the host immune system and allow exploring extrahepatic transplantation sites. We report on the characterization and creation of porous polyvinylidene fluoride (PVDF) membrane-based devices intended for islet and beta-cell transplantation. We hypothesize that by incorporating polyvinyl-pyrrolidone (PVP) into a PVDF solution the permeability of PVDF membranes for insulin and glucose can be improved by solvent-non solvent casting to create submicrometer porous films. We show that the use of water-soluble PVP, can significantly increase glucose diffusion through these membranes while still having the ability to block immune cells from migrating through these membranes. Human donor islets loaded into devices made from these thin PVDF/PVP membranes showed a 92 ± 4% viability after 8 days similar to their free-floating counterparts. The glucose responsiveness of human donor islets encapsulated inside PVDF/PVP membrane-based devices was significantly improved compared to islets seeded in devices made from PVDF membranes without PVP, with a stimulation index of 3.2 for PVDF/PVP devices and 1.3 for PVDF-alone devices at day 8. Our data show that by addition of PVP as pore forming agent during membrane fabrication at a specific ratio the diffusion characteristics can be tuned such that human islet function in these closed macrodevices, can be kept at the same level as non-encapsulated islets, while the membrane can still serve as a protective barrier preventing the entry of primary human macrophages and damaging beta cells.
1型糖尿病（T1D）患者终生依赖胰岛素治疗来控制血糖水平。临床胰岛移植（CIT）是一种替代外源性胰岛素注射的基于细胞的治疗方法。目前，CIT的广泛应用受到限制，因为长期使用免疫抑制药物来防止供体细胞排斥存在风险。一种免疫保护的大封装装置可以保护异体胰岛细胞免受宿主免疫系统的攻击，并允许探索肝外移植部位。我们报告了用于胰岛和β细胞移植的基于多孔聚偏二氟乙烯（PVDF）膜的装置的表征和制备。我们假设，通过将聚乙烯吡咯烷酮（PVP）加入PVDF溶液中，通过溶剂-非溶剂浇铸来制备亚微米多孔膜，可以提高PVDF膜对胰岛素和葡萄糖的渗透性。我们表明，使用水溶性PVP可以显著增加葡萄糖通过这些膜的扩散，同时仍然能够阻止免疫细胞穿过这些膜。加载到由这些薄PVDF/PVP膜制成的装置中的人类供体胰岛在8天后的存活率为92±4%，与自由漂浮的胰岛相似。与接种在由不含PVP的PVDF膜制成的装置中的胰岛相比，封装在基于PVDF/PVP膜的装置中的人类供体胰岛的葡萄糖反应性显著提高，在第8天，PVDF/PVP装置的刺激指数为3.2，而仅PVDF装置的刺激指数为1.3。我们的数据表明，在膜制造过程中以特定比例添加PVP作为成孔剂，可以调节扩散特性，使得这些封闭的大装置中的人类胰岛功能可以保持在与未封装胰岛相同的水平，同时该膜仍然可以作为保护屏障，防止原代人类巨噬细胞进入并损害β细胞。
