iPSC-derived cranial neural crest-like cells can replicate dental pulp tissue with the aid of angiogenic hydrogel.

iPSC-derived cranial neural crest-like cells can replicate dental pulp tissue with the aid of angiogenic hydrogel.
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DOI:
10.1016/j.bioactmat.2021.11.014
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发表时间:
2022-08
影响因子:
18.9
通讯作者:
Shimizu E
Shimizu E
中科院分区:
工程技术1区
文献类型:
--
作者:
Kobayashi Y;Nouet J;Baljinnyam E;Siddiqui Z;Fine DH;Fraidenraich D;Kumar VA;Shimizu E

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牙髓在维持牙齿健康方面具有不可替代的作用,其再生是再生牙髓学的首要目标。本研究旨在利用颅神经嵴(CNC)样细胞(CNCLC)复制牙髓组织的特征;这些细胞是通过修改先前建立的从诱导多能干细胞 (iPSC) 中衍生 NC 样细胞的方法的几个步骤来生成的。 CNC是脊椎动物胚胎中神经嵴的前部区域,其中包含牙髓细胞或成牙本质细胞的原基。产生的 CNCLC 显示主要 CNC 标记基因上调约 2.5-12,000 倍。此外,CNCLC 表现出显着的成牙本质细胞分化能力,特别是在用成纤维细胞生长因子 (FGF) FGF4 和 FGF9 组合处理时。与骨形态发生蛋白 4 (BMP4) 治疗相比,FGF 诱导的成牙本质细胞标记基因提高了 1.7-5.0 倍。在小鼠皮下植入模型中,CNCLC 短暂地与 FGF4 + FGF9 一起复制了牙髓组织特征,例如含有成牙本质细胞样细胞、牙本质样层和由血管生成自组装肽水凝胶 (SAPH) SLan 诱导的大量新生血管。 SLan 在根管空间中充当多功能生物相容性支架。这项研究证明了再生医学和 SAPH 技术之间的成功合作。颅神经嵴样细胞 (CNCLC) 是通过简化先前建立的从 iPSC 衍生神经嵴样细胞的方法而产生的。产生的 CNCLC 显示主要 CNC 标记基因上调约 12,000 倍。成纤维细胞生长因子 FGF4 和 FGF9 的组合比 BMP4 更有效地诱导 CNCLC 向成牙本质细胞分化。在小鼠皮下植入模型中,CNCLC 在血管生成水凝胶 SLan 的帮助下复制了含有大量新生血管的牙髓特征。
The dental pulp has irreplaceable roles in maintaining healthy teeth and its regeneration is a primary aim of regenerative endodontics. This study aimed to replicate the characteristics of dental pulp tissue by using cranial neural crest (CNC)-like cells (CNCLCs); these cells were generated by modifying several steps of a previously established method for deriving NC-like cells from induced pluripotent stem cells (iPSCs). CNC is the anterior region of the neural crest in vertebrate embryos, which contains the primordium of dental pulp cells or odontoblasts. The produced CNCLCs showed approximately 2.5–12,000-fold upregulations of major CNC marker genes. Furthermore, the CNCLCs exhibited remarkable odontoblastic differentiation ability, especially when treated with a combination of the fibroblast growth factors (FGFs) FGF4 and FGF9. The FGFs induced odontoblast marker genes by 1.7–5.0-fold, as compared to bone morphogenetic protein 4 (BMP4) treatment. In a mouse subcutaneous implant model, the CNCLCs briefly fated with FGF4 + FGF9 replicated dental pulp tissue characteristics, such as harboring odontoblast-like cells, a dentin-like layer, and vast neovascularization, induced by the angiogenic self-assembling peptide hydrogel (SAPH), SLan. SLan acts as a versatile biocompatible scaffold in the canal space. This study demonstrated a successful collaboration between regenerative medicine and SAPH technology. Cranial neural crest like cells (CNCLCs) were generated by simplifying a previously established method for deriving neural crest-like cells from iPSCs. The produced CNCLCs showed approximately ∼12,000-fold upregulations of major CNC marker genes. The combination of fibroblast growth factors, FGF4 and FGF9, induced the CNCLCs toward odontoblastic differentiation more effectively than BMP4. In a mice subcutaneous implant model, the CNCLCs replicated the characteristics of dental pulp harboring vast neovascularization with the aid of the angiogenic hydrogel, SLan.
一种自组装的肽水凝胶,用于细胞因子隔离。
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期刊: Restorative dentistry & endodontics
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Seo MS;Hwang KG;Kim H;Baek SH
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DOI: 10.1371/journal.pone.0059056
发表时间: 2013
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影响因子: 3.7
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