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壳聚糖水凝胶联合二甲双胍促进牙龈间充质干细胞向神经元样细胞分化。

Chitosan Hydrogel Supplemented with Metformin Promotes Neuron-like Cell Differentiation of Gingival Mesenchymal Stem Cells.

机构信息

School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing 100083, China.

Daxing Research Institute, University of Science and Technology Beijing, Beijing 100083, China.

出版信息

Int J Mol Sci. 2022 Mar 18;23(6):3276. doi: 10.3390/ijms23063276.

DOI:10.3390/ijms23063276
PMID:35328696
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8955038/
Abstract

Human gingival mesenchymal stem cells (GMSCs) are derived from migratory neural crest stem cells and have the potential to differentiate into neurons. Metformin can inhibit stem-cell aging and promotes the regeneration and development of neurons. In this study, we investigated the potential of metformin as an enhancer on neuronal differentiation of GMSCs in the growth environment of chitosan hydrogel. The crosslinked chitosan/β-glycerophosphate hydrogel can form a perforated microporous structure that is suitable for cell growth and channels to transport water and macromolecules. GMSCs have powerful osteogenic, adipogenic and chondrogenic abilities in the induction medium supplemented with metformin. After induction in an induction medium supplemented with metformin, Western blot and immunofluorescence results showed that GMSCs differentiated into neuron-like cells with a significantly enhanced expression of neuro-related markers, including Nestin (NES) and β-Tubulin (TUJ1). Proteomics was used to construct protein profiles in neural differentiation, and the results showed that chitosan hydrogels containing metformin promoted the upregulation of neural regeneration-related proteins, including ATP5F1, ATP5J, NADH dehydrogenase (ubiquinone) Fe-S protein 3 (NDUFS3), and Glutamate Dehydrogenase 1 (GLUD1). Our results help to promote the clinical application of stem-cell neural regeneration.

摘要

人牙龈间充质干细胞（GMSCs）来源于迁移的神经嵴干细胞，具有分化为神经元的潜能。二甲双胍可以抑制干细胞衰老，促进神经元的再生和发育。在这项研究中，我们研究了二甲双胍作为一种增强剂，在壳聚糖水凝胶的生长环境中对 GMSCs 向神经元分化的潜力。交联壳聚糖/β-甘油磷酸水凝胶可以形成适合细胞生长的多孔微结构和运输水和大分子的通道。在补充有二甲双胍的诱导培养基中，GMSCs 具有强大的成骨、成脂和成软骨能力。在补充有二甲双胍的诱导培养基中诱导后，Western blot 和免疫荧光结果表明，GMSCs 分化为具有明显增强的神经相关标志物表达的神经元样细胞，包括巢蛋白（NES）和微管相关蛋白 2（TUJ1）。蛋白质组学用于构建神经分化的蛋白质图谱，结果表明，含有二甲双胍的壳聚糖水凝胶促进了神经再生相关蛋白的上调，包括 ATP5F1、ATP5J、NADH 脱氢酶（泛醌）Fe-S 蛋白 3（NDUFS3）和谷氨酸脱氢酶 1（GLUD1）。我们的研究结果有助于促进干细胞神经再生的临床应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/39b8/8955038/f70d2580f8c2/ijms-23-03276-sch002.jpg
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