Generation of periodontal ligament stem cells from human iPSCs with a chemically defined condition
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ORIGINAL PAPER
Generation of periodontal ligament stem cells from human iPSCs with a chemically defined condition Yue Wang1 · Yongmei Hua1 Received: 12 March 2019 / Accepted: 5 June 2020 © Akadémiai Kiadó Zrt. 2020
Abstract Human periodontal ligament stem cells (PDLSCs) play an important role in periodontal tissue regeneration. The generation of PDLSCs from human induced pluripotent stem cells (iPSCs) by simulating the development pattern of PDLSCs in vivo provided a new way to obtain a large and stable source of PDLSCs. However, animal-derived components were still necessary for current differentiation protocols, which could cause safety and ethical problems and hinder the clinical application of iPSCs-derived PDLSCs. Here, we established a novel protocol to induce iPSCs into PDLSCs by chemically defined conditions. We first induced iPSCs into neural crest-like cells by inhibiting TGF-β pathway, BMP pathway and Notch pathway using SB431542, LDN and DAPT, respectively. The iPSC-induced neural crest-like cells were further cultured in chemically defined medium containing recombinant human bFGF as well as the rho-associated protein kinase inhibitor Y27632 to generate PDLSCs. The characteristics of iPSCs-derived PDLSCs and the bi-potentiality of osteogenesis and adipogenesis differentiation were verified in vitro. The establishment of the chemically defined differentiation system breaks through the limitation brought from animal-derived components and enables us to obtain a large number of PDLSCs, which holds a significant value to the research and treatment of periodontal diseases. Keywords Periodontal ligament stem cells · Induced pluripotent stem cells · Chemically defined differentiation system
Introduction Periodontitis is a worldwide common disease related to the interaction between oral bacteria and host immunity, which can lead to irreversible destruction of periodontal tissues such as gingiva, periodontal ligament and alveolar bone and ultimately lead to tooth loss. Periodontitis is also widely reported to be associated with systemic diseases [2, 5]. The goal of periodontal treatment is to control inflammation, block disease progression and restore the appearance and function of periodontal tissue. Traditional periodontal basic therapy is competent to control inflammation and block disease progression. However, there is no good treatment to regenerate the periodontal tissue. Clinical experts have made many important attempts in tissue regeneration, such * Yongmei Hua [email protected] 1
Department of Orthodontics, School of Stomatology, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Tongji University, Shanghai, China
as tissue regeneration/guided bone regeneration (GTR/GBR) and growth factor-based therapy [8, 27]. However, the clinical prognosis is not ideal, so it is important to explore more effective tissue repair methods. Previous studies have shown that periodontal ligament contains multifunctional stem cells, which were named periodontal ligament stem cells (
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