Graduate School of Medicine, Science and Technology, Shinshu University, Ueda, Nagano, Japan.
Graduate School of Science and Technology, Shinshu University, Ueda, Nagano, Japan; Center for Genetic Analysis of Behavior, National Institute for Physiological Sciences, Okazaki, Aichi, Japan.
Transplant Proc. 2021 Jun;53(5):1744-1750. doi: 10.1016/j.transproceed.2021.04.012. Epub 2021 May 26.
Islet transplantation is a promising option for the clinical treatment of insulin-dependent diabetes, but a reliable islet cryopreservation/transplantation protocol should be established to overcome the donor shortage. The current study reports that a silk fibroin (SF) sponge disk can be used as a cryodevice for vitrification of large quantity pancreatic islets and the scaffold for subsequent subrenal transplantation in a rat model. The marginal islet mass (550 islet equivalents [IEQs]) on an SF sponge disk was vitrified-warmed and transplanted beneath the kidney capsule of a streptozotocin-induced diabetic rat with or without vascular endothelial growth factor (VEGF). Subrenal transplantation (no scaffold) of 550 IEQ fresh islets and post-warm islets vitrified on a nylon mesh device resulted in achieving euglycemia of recipient rats at 60% and 0%, respectively. Transplantation of 550 IEQ islets vitrified-warmed on an SF sponge disk failed to achieve euglycemia of recipient rats (0%), but the VEGF inclusion in the SF sponge disk contributed to acquiring the euglycemic recipients (33%). All cured recipient rats regained hyperglycemia after nephrectomy, and the histopathologic analysis exhibited a well-developing blood vessel network into the islet engrafts. Thus, an SF sponge disc was successively available as the cryodevice for islet vitrification, the transporter of the angiogenic VEGF, and the scaffold for subrenal transplantation in the rat model.
胰岛移植是治疗胰岛素依赖型糖尿病的一种很有前途的选择,但需要建立一个可靠的胰岛冻存/移植方案,以克服供体短缺的问题。本研究报告称,丝素蛋白(SF)海绵片可作为大量胰岛玻璃化的冷冻设备,以及随后在大鼠模型中肾下移植的支架。在链脲佐菌素诱导的糖尿病大鼠的肾下囊下,SF 海绵片上的边缘胰岛质量(550 胰岛当量[IEQs])进行玻璃化-复温,并在有无血管内皮生长因子(VEGF)的情况下进行移植。550IEQ 新鲜胰岛和在尼龙网装置上进行玻璃化复温的胰岛进行肾下移植(无支架),使受体大鼠的血糖正常化分别达到 60%和 0%。550IEQ 胰岛在 SF 海绵片上玻璃化复温后移植未能使受体大鼠血糖正常化(0%),但 SF 海绵片中的 VEGF 有助于获得血糖正常化的受体(33%)。所有治愈的受体大鼠在肾切除后恢复高血糖,组织病理学分析显示胰岛移植物中形成了发达的血管网络。因此,SF 海绵片可依次用作胰岛玻璃化的冷冻设备、血管生成 VEGF 的转运体和大鼠模型中肾下移植的支架。