School of Life Science, Shanxi Datong University, Datong, Shanxi, China; Institute of Applied Biotechnology, Shanxi Datong University, Datong, Shanxi, China.
School of Chemical Engineering, Shanxi Datong University, Datong, Shanxi, China.
Mater Sci Eng C Mater Biol Appl. 2019 Apr;97:593-601. doi: 10.1016/j.msec.2018.12.062. Epub 2018 Dec 19.
Diabetes mellitus is an epidemic worldwide. Pancreatic stem cells can be induced to differentiate into insulin-secreting cells, this method is an effective way to solve the shortage of islet donor. Poly (lactic acid-co-glycolic acid (PLGA) copolymer is an excellent scaffold for tissue engineering as it presents good biocompatibility and film forming properties. In this study, we adopted biological methods, using fibroblast-coated PLGA diaphragm to form a biological membrane, and then pancreatic stem cells were cultured on the fibroblast-modified PLGA membrane and the two-step induction method was utilized to induce the differentiation of pancreatic stem cells into insulin-secreting cells. The proliferation and differentiation of pancreatic stem cells on the fibroblast-modified PLGA membrane as well as the expression of genes related to the differentiation of pancreatic stem cells were examined in both normal and induced cultures to explore the potential of fibroblast-modified PLGA membrane for the transplantation to treat diabetes mellitus. The results indicated that fibroblasts can effectively improve the cell compatibility and histocompatibility of the PLGA membrane and promote the proliferation and differentiation of pancreatic stem cells. After induction, real-time fluorescence quantitative PCR (FQRT-PCR) results showed there were more Notch receptors and its ligands expressed in the membranes of pancreatic stem cells than non-induced pancreatic stem cells or fibroblast. Semiconductor quantum dot coupled-anti-complex probe experiments revealed that induced pancreatic stem cells had higher expression levels of Notch 2 and Delta-like 1 than non-induced ones, which may regulate the expression of Neurogenin-3 (Ngn3) and Hairy/Enhancer of split-1 gene (Hes1) through Notch signaling interaction between fibroblasts and pancreatic stem cells as well as enhance the proliferation of pancreatic stem cells and their differentiation into insulin-secreting cells. Further, our study suggests that the fibroblast-modified PLGA membrane can be used as matrix material composed of pancreatic stem cells or other stem cells to construct artificial islet tissue for the treatment of diabetes mellitus.
糖尿病是一种全球性的流行病。诱导胰腺干细胞分化为胰岛素分泌细胞是解决胰岛供体短缺的有效方法。聚（乳酸-共-羟基乙酸）（PLGA）共聚物是组织工程的优秀支架，因为它具有良好的生物相容性和成膜性能。在这项研究中，我们采用了生物学方法，用成纤维细胞包被的 PLGA 膜片形成生物膜，然后在成纤维细胞修饰的 PLGA 膜上培养胰腺干细胞，并采用两步诱导法诱导胰腺干细胞分化为胰岛素分泌细胞。在正常和诱导培养中，检查了胰腺干细胞在成纤维细胞修饰的 PLGA 膜上的增殖和分化以及与胰腺干细胞分化相关的基因的表达，以探讨成纤维细胞修饰的 PLGA 膜在移植治疗糖尿病中的潜力。结果表明，成纤维细胞可以有效地提高 PLGA 膜的细胞相容性和组织相容性，并促进胰腺干细胞的增殖和分化。诱导后，实时荧光定量 PCR（FQRT-PCR）结果显示，诱导后的胰腺干细胞膜中 Notch 受体及其配体的表达明显高于未诱导的胰腺干细胞或成纤维细胞。半导体量子点偶联抗复合物探针实验显示，诱导后的胰腺干细胞 Notch2 和 Delta-like1 的表达水平明显高于未诱导的胰腺干细胞，这可能通过成纤维细胞和胰腺干细胞之间的 Notch 信号相互作用调节神经基因-3（Ngn3）和 Hairy/增强子分裂-1 基因（Hes1）的表达，并增强胰腺干细胞的增殖及其向胰岛素分泌细胞的分化。此外，我们的研究表明，成纤维细胞修饰的 PLGA 膜可以作为由胰腺干细胞或其他干细胞组成的基质材料，用于构建用于治疗糖尿病的人工胰岛组织。
