IRCCS Centro Neurolesi "Bonino-Pulejo," Via Provinciale Palermo, Contrada Casazza, 98124 Messina, Italy.
Stem Cells and Regenerative Medicine Laboratory, Department of Medical, Oral and Biotechnological Sciences, University "G. D'Annunzio," Chieti-Pescara, via dei Vestini, 31, 66100, Chieti, Italy.
J Biomed Mater Res A. 2018 Jan;106(1):126-137. doi: 10.1002/jbm.a.36213. Epub 2017 Sep 26.
The combined approach of mesenchymal stem cells (MSCs) and scaffolds has been proposed as a potential therapeutic tool for the treatment of neurodegenerative diseases. Indeed, even if MSCs can promote neuronal regeneration, replacing lost neurons or secreting neurotrophic factors, many limitations still exist for their application in regenerative medicine, including the low survival and differentiation rate. The scaffolds, by mimicking the endogenous microenvironment, have shown to promote cell survival, proliferation, and differentiation. In this work, gingival mesenchymal stem cells (GMSCs), isolated from healthy donors, were expanded in vitro, by culturing them adherent in plastic dishes (CTR-GMSCs) or on a poly(lactic acid) scaffold (SC-GMSCs). In order to evaluate the survival and the neurogenic differentiation potential, we performed a comparative transcriptomic analysis between CTR-GMSCs and SC-GMSCs by next generation sequencing. We found that SC-GMSCs showed an increased expression of neurogenic and prosurvival genes. In particular, genes involved in neurotrophin signaling and PI3K/Akt pathways were upregulated. On the contrary, proapoptotic and negative regulator of neuronal growth genes were downregulated. Moreover, nestin and GAP-43 protein levels increased in SC-GMSCs, confirming the neurogenic commitment of these cells. In conclusion, the scaffold, providing a trophic support for MSCs, may promote GMSCs differentiation toward a neuronal phenotype and survival. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 126-137, 2018.
间质干细胞(MSCs)与支架的联合应用被提出作为治疗神经退行性疾病的一种有潜力的治疗手段。的确,即使 MSCs 可以促进神经元再生、替代丢失的神经元或分泌神经营养因子,但其在再生医学中的应用仍然存在许多限制,包括低存活率和分化率。支架通过模拟内源性微环境,已被证明可以促进细胞存活、增殖和分化。在这项工作中,从健康供体中分离出的牙龈间充质干细胞(GMSCs),通过在塑料培养皿中贴壁培养(CTR-GMSCs)或在聚乳酸支架(SC-GMSCs)上培养来进行体外扩增。为了评估细胞的存活和神经发生分化潜能,我们通过下一代测序对 CTR-GMSCs 和 SC-GMSCs 进行了比较转录组分析。我们发现 SC-GMSCs 表现出神经发生和生存相关基因的表达增加。特别是,涉及神经营养因子信号和 PI3K/Akt 通路的基因上调。相反,促凋亡和神经元生长的负调控基因下调。此外,SC-GMSCs 中的巢蛋白和 GAP-43 蛋白水平增加,证实了这些细胞的神经发生特性。总之,支架为 MSCs 提供了营养支持,可能促进 GMSCs 向神经元表型分化和存活。©2017Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 126-137, 2018.