Lan Tianshu, Guo Jingyi, Bai Xiaoming, Huang Zengjiong, Wei Zhimin, Du Guicheng, Yan Guoliang, Weng Lebin, Yi Xue
Xiamen Medical College, Xiamen city, Fujian Province, China.
Key laboratory of functional and clinical translational medicine, Fujian province university, Xiamen Medical College, Xiamen city, China.
J Appl Biomater Funct Mater. 2020 Jan-Dec;18:2280800020963473. doi: 10.1177/2280800020963473.
A potential solution for islet transplantation and drug discovery vis-à-vis treating diabetes is the production of functional islets in a three-dimensional extracellular matrix. Although several scaffold materials have been reported as viable candidates, a clinically applicable one that is injectable and can maintain long-term functionality and survival of islet pancreatic beta-cells (β-cells) is far from being established.
In the current study, we evaluated a ready-to-use and injectable hydrogel's impact on β-cells' function and viability, both in vitro and in vivo. We found that β-cells in high concentration with hydrogels functionalized via Arg-Gly-Asp (RGD) demonstrated better viability and insulin secretory capacity in vitro. Moreover, it is a biocompatible hydrogel that can maintain β-cell proliferation and vascularization without stimulating inflammation after subcutaneous injection. Meanwhile, modifying the hydrogel with RGD can maintain β-cells' secretion of insulin, regulating the blood glucose levels of mice with streptozotocin-induced diabetes.
Thus, these preliminary results indicate that this RGD-modified hydrogel is a potential extracellular matrix for islet transplantation at extrahepatic sites, and they also provide a reference for future tissue engineering study.
通过在三维细胞外基质中生成功能性胰岛来解决胰岛移植和药物研发方面的糖尿病治疗问题。尽管已有几种支架材料被报道为可行的候选材料,但一种可注射且能维持胰岛胰腺β细胞长期功能和存活的临床适用材料尚未确立。
在本研究中,我们评估了一种即用型可注射水凝胶在体外和体内对β细胞功能及活力的影响。我们发现,与通过精氨酸-甘氨酸-天冬氨酸(RGD)功能化的水凝胶高浓度混合的β细胞在体外表现出更好的活力和胰岛素分泌能力。此外,它是一种生物相容性水凝胶,皮下注射后可维持β细胞增殖和血管生成,且不会引发炎症。同时,用RGD修饰水凝胶可维持β细胞的胰岛素分泌,调节链脲佐菌素诱导的糖尿病小鼠的血糖水平。
因此,这些初步结果表明,这种RGD修饰的水凝胶是肝外部位胰岛移植的潜在细胞外基质,也为未来的组织工程研究提供了参考。