由人类多能干细胞产生的颚骨样器官

IF 26.8 1区 医学 Q1 ENGINEERING, BIOMEDICAL
Souta Motoike, Yoshiko Inada, Junya Toguchida, Mikihito Kajiya, Makoto Ikeya
{"title":"由人类多能干细胞产生的颚骨样器官","authors":"Souta Motoike, Yoshiko Inada, Junya Toguchida, Mikihito Kajiya, Makoto Ikeya","doi":"10.1038/s41551-025-01419-3","DOIUrl":null,"url":null,"abstract":"<p>Engineering jawbone tissues from pluripotent stem cells presents a challenge owing to the lack of protocols for selectively inducing the jawbone progenitor, the first pharyngeal arch (PA1) ectomesenchyme, and for recapitulating three-dimensional osteocyte networks. Here we present a method for generating jawbone-like organoids from human induced pluripotent stem cells through PA1 ectomesenchyme of the mandibular prominence (mdEM). A three-dimensional culture system enables sequential differentiation of induced pluripotent stem cells into neural crest cells and mdEM. The mdEM exhibits proximal–distal patterning from the centre outwards, mirroring mandibular development. The introduction of exogenous pharyngeal epithelial signals induces mandibular prominence-specific regional patterning in the mdEM. When cultured under osteogenic conditions, the mdEM forms jawbone-like organoids comprising osteoblasts and network-forming osteocytes embedded in self-produced mineralized bone matrices. Moreover, these organoids promote bone regeneration when transplanted into jaws containing bone defects and recapitulate phenotypes of osteogenesis imperfecta, a genetic disorder characterized by fragile bones, using patient-derived induced pluripotent stem cells. Our protocols establish a foundation for investigating human jaw embryology and pathophysiology.</p>","PeriodicalId":19063,"journal":{"name":"Nature Biomedical Engineering","volume":"13 1","pages":""},"PeriodicalIF":26.8000,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Jawbone-like organoids generated from human pluripotent stem cells\",\"authors\":\"Souta Motoike, Yoshiko Inada, Junya Toguchida, Mikihito Kajiya, Makoto Ikeya\",\"doi\":\"10.1038/s41551-025-01419-3\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>Engineering jawbone tissues from pluripotent stem cells presents a challenge owing to the lack of protocols for selectively inducing the jawbone progenitor, the first pharyngeal arch (PA1) ectomesenchyme, and for recapitulating three-dimensional osteocyte networks. Here we present a method for generating jawbone-like organoids from human induced pluripotent stem cells through PA1 ectomesenchyme of the mandibular prominence (mdEM). A three-dimensional culture system enables sequential differentiation of induced pluripotent stem cells into neural crest cells and mdEM. The mdEM exhibits proximal–distal patterning from the centre outwards, mirroring mandibular development. The introduction of exogenous pharyngeal epithelial signals induces mandibular prominence-specific regional patterning in the mdEM. When cultured under osteogenic conditions, the mdEM forms jawbone-like organoids comprising osteoblasts and network-forming osteocytes embedded in self-produced mineralized bone matrices. Moreover, these organoids promote bone regeneration when transplanted into jaws containing bone defects and recapitulate phenotypes of osteogenesis imperfecta, a genetic disorder characterized by fragile bones, using patient-derived induced pluripotent stem cells. Our protocols establish a foundation for investigating human jaw embryology and pathophysiology.</p>\",\"PeriodicalId\":19063,\"journal\":{\"name\":\"Nature Biomedical Engineering\",\"volume\":\"13 1\",\"pages\":\"\"},\"PeriodicalIF\":26.8000,\"publicationDate\":\"2025-07-02\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Nature Biomedical Engineering\",\"FirstCategoryId\":\"5\",\"ListUrlMain\":\"https://doi.org/10.1038/s41551-025-01419-3\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ENGINEERING, BIOMEDICAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature Biomedical Engineering","FirstCategoryId":"5","ListUrlMain":"https://doi.org/10.1038/s41551-025-01419-3","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENGINEERING, BIOMEDICAL","Score":null,"Total":0}
引用次数: 0

摘要

由于缺乏选择性诱导颌骨祖细胞、第一咽弓(PA1)外间充质和重建三维骨细胞网络的方案,从多能干细胞工程颌骨组织提出了一个挑战。在此,我们提出了一种利用人诱导多能干细胞通过下颌突(mdEM)的PA1外切间充质生成颚骨样器官的方法。三维培养系统使诱导多能干细胞依次分化为神经嵴细胞和中西医结合细胞。mdEM从中心向外呈现近端-远端模式,反映下颌发育。外源性咽上皮信号的引入诱导下颌突起特异性区域模式。当在成骨条件下培养时,mdEM形成颌骨样器官,包括成骨细胞和嵌入自产矿化骨基质的网状骨细胞。此外,当使用患者来源的诱导多能干细胞将这些类器官移植到含有骨缺损和成骨不完全性(一种以脆弱骨骼为特征的遗传疾病)重现表型的颌骨时,这些类器官促进骨再生。我们的研究方案为研究人类颌骨胚胎学和病理生理学奠定了基础。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Jawbone-like organoids generated from human pluripotent stem cells

Jawbone-like organoids generated from human pluripotent stem cells

Engineering jawbone tissues from pluripotent stem cells presents a challenge owing to the lack of protocols for selectively inducing the jawbone progenitor, the first pharyngeal arch (PA1) ectomesenchyme, and for recapitulating three-dimensional osteocyte networks. Here we present a method for generating jawbone-like organoids from human induced pluripotent stem cells through PA1 ectomesenchyme of the mandibular prominence (mdEM). A three-dimensional culture system enables sequential differentiation of induced pluripotent stem cells into neural crest cells and mdEM. The mdEM exhibits proximal–distal patterning from the centre outwards, mirroring mandibular development. The introduction of exogenous pharyngeal epithelial signals induces mandibular prominence-specific regional patterning in the mdEM. When cultured under osteogenic conditions, the mdEM forms jawbone-like organoids comprising osteoblasts and network-forming osteocytes embedded in self-produced mineralized bone matrices. Moreover, these organoids promote bone regeneration when transplanted into jaws containing bone defects and recapitulate phenotypes of osteogenesis imperfecta, a genetic disorder characterized by fragile bones, using patient-derived induced pluripotent stem cells. Our protocols establish a foundation for investigating human jaw embryology and pathophysiology.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Nature Biomedical Engineering
Nature Biomedical Engineering Medicine-Medicine (miscellaneous)
CiteScore
45.30
自引率
1.10%
发文量
138
期刊介绍: Nature Biomedical Engineering is an online-only monthly journal that was launched in January 2017. It aims to publish original research, reviews, and commentary focusing on applied biomedicine and health technology. The journal targets a diverse audience, including life scientists who are involved in developing experimental or computational systems and methods to enhance our understanding of human physiology. It also covers biomedical researchers and engineers who are engaged in designing or optimizing therapies, assays, devices, or procedures for diagnosing or treating diseases. Additionally, clinicians, who make use of research outputs to evaluate patient health or administer therapy in various clinical settings and healthcare contexts, are also part of the target audience.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信