School of Life Science and Technology, Tokyo Institute of Technology, Yokohama, Japan.
Daiichi Sankyo Co., Ltd., Shinagawa-ku, Japan.
Cell Transplant. 2024 Jan-Dec;33:9636897241277980. doi: 10.1177/09636897241277980.
Type 1 diabetes mellitus (T1DM) affects 8.4 million people worldwide, with patients primarily relying on exogenous insulin injections to maintain blood glucose levels. Islet transplantation via the portal vein has allowed for the direct internal release of insulin by glucose-sensitive islets. However, this method might not be desirable for future cell therapy transplanting pluripotent stem cell-derived β cells, facing challenges including difficulties in cell retrieval and graft loss due to the instant blood-mediated inflammatory reaction (IBMIR). Here, we established a subcutaneous transplantation protocol using an atelocollagen sponge as a scaffold. While the subcutaneous site has many advantages, the lack of a vascular bed limits its application. To address this issue, we performed angiogenesis stimulation at the transplantation site using bFGF absorbed in a gelatin sponge (Spongel), significantly improving the microvascular area. Our in vivo experiments also revealed angiogenesis stimulation is crucial for reversing hyperglycemia in streptozotocin (STZ)-induced diabetic mice. In addition to the angiogenic treatment, an atelocollagen sponge is used to carry the islets and helps avoid graft leakage. With 800 mouse islets delivered by the atelocollagen sponge, the STZ-induced diabetic mice showed a reversal of hyperglycemia and normalized glucose intolerance. Their normoglycemia was maintained until the graft was removed. Analysis of the harvested islet grafts exhibited a high vascularization and preserved morphologies, suggesting that using an atelocollagen sponge as a scaffold helps maintain the viability of the islet grafts.
1 型糖尿病（T1DM）影响全球 8400 万人，患者主要依赖外源性胰岛素注射来维持血糖水平。门静脉胰岛移植使葡萄糖敏感胰岛能够直接内部释放胰岛素。然而，对于未来的细胞治疗移植多能干细胞衍生的β细胞来说，这种方法可能并不理想，因为它面临着细胞回收和移植物丢失的困难，这是由于即时的血液介导的炎症反应（IBMIR）引起的。在这里，我们建立了一种使用脱细胞胶原海绵作为支架的皮下移植方案。虽然皮下部位有许多优点，但缺乏血管床限制了其应用。为了解决这个问题，我们在移植部位使用 bFGF 吸收在明胶海绵（Spongel）中进行血管生成刺激，显著改善了微血管面积。我们的体内实验还表明，血管生成刺激对于逆转链脲佐菌素（STZ）诱导的糖尿病小鼠的高血糖至关重要。除了血管生成治疗外，脱细胞胶原海绵还用于携带胰岛并有助于避免移植物泄漏。通过脱细胞胶原海绵输送 800 个胰岛，STZ 诱导的糖尿病小鼠的高血糖得到逆转，葡萄糖耐量正常化。它们的正常血糖水平一直维持到移植物被移除。对收获的胰岛移植物的分析显示出高度的血管化和保留的形态，表明使用脱细胞胶原海绵作为支架有助于维持胰岛移植物的活力。
