Tsutsui Takeo W
Department of Pharmacology, School of Life Dentistry at Tokyo, The Nippon Dental University, Tokyo, Japan.
Stem Cells Cloning. 2020 Feb 13;13:33-42. doi: 10.2147/SCCAA.S166759. eCollection 2020.
Dental pulp stem cells (DPSCs) have a high capacity for differentiation and the ability to regenerate a dentin/pulp-like complex. Numerous studies have provided evidence of DPSCs' differentiation capacity, such as in neurogenesis, adipogenesis, osteogenesis, chondrogenesis, angiogenesis, and dentinogenesis. The molecular mechanisms and functions of DPSCs' differentiation process are affected by growth factors and scaffolds. For example, growth factors such as basic fibroblast growth factor (bFGF), transforming growth factor-β (TGF-β), nerve growth factor (NGF), platelet-derived growth factor (PDGF), and bone morphogenic proteins (BMPs) influence DPSC fate, including in differentiation, cell proliferation, and wound healing. In addition, several types of scaffolds, such as collagen, hydrogel, decellularized bioscaffold, and nanofibrous spongy microspheres, have been used to characterize DPSC cellular attachment, migration, proliferation, differentiation, and functions. An appropriate combination of growth factors and scaffolds can enhance the differentiation capacity of DPSCs, in terms of optimizing not only dental-related expression but also dental pulp morphology. For a cell-based clinical approach, focus has been placed on the tissue engineering triad [cells/bioactive molecules (growth factors)/scaffolds] to characterize DPSCs. It is clear that a deep understanding of the mechanisms of stem cells, including their aging, self-renewal, microenvironmental homeostasis, and differentiation correlated with cell activity, the energy for which is provided from mitochondria, should provide new approaches for DPSC research and therapeutics. Mitochondrial functions and dynamics are related to the direction of stem cell differentiation, including glycolysis, oxidative phosphorylation, mitochondrial metabolism, mitochondrial transcription factor A (TFAM), mitochondrial elongation, and mitochondrial fusion and fission proteins. This review summarizes the effects of major growth factors and scaffolds for regenerating dentin/pulp-like complexes, as well as elucidating mitochondrial properties of DPSCs for the development of advanced applications research.
牙髓干细胞（DPSCs）具有高分化能力以及再生牙本质/牙髓样复合体的能力。大量研究已提供了DPSCs分化能力的证据，比如在神经发生、脂肪生成、骨生成、软骨生成、血管生成和牙本质生成方面。DPSCs分化过程的分子机制和功能受生长因子和支架的影响。例如，碱性成纤维细胞生长因子（bFGF）、转化生长因子-β（TGF-β）、神经生长因子（NGF）、血小板衍生生长因子（PDGF）和骨形态发生蛋白（BMPs）等生长因子会影响DPSC的命运，包括分化、细胞增殖和伤口愈合。此外，几种类型的支架，如胶原蛋白、水凝胶、脱细胞生物支架和纳米纤维海绵微球，已被用于表征DPSC的细胞附着、迁移、增殖、分化和功能。生长因子和支架的适当组合可以增强DPSCs的分化能力，不仅优化与牙齿相关的表达，还能优化牙髓形态。对于基于细胞的临床方法，重点已放在组织工程三元组[细胞/生物活性分子（生长因子）/支架]来表征DPSCs。显然，深入了解干细胞的机制，包括其衰老、自我更新、微环境稳态以及与细胞活性相关的分化，而细胞活性的能量由线粒体提供，应该能为DPSC研究和治疗提供新方法。线粒体功能和动力学与干细胞分化方向相关，包括糖酵解、氧化磷酸化、线粒体代谢、线粒体转录因子A（TFAM）、线粒体延长以及线粒体融合和裂变蛋白。本综述总结了主要生长因子和支架对再生牙本质/牙髓样复合体的影响，以及阐明DPSCs的线粒体特性以开展高级应用研究。
