Programmatic introduction of parenchymal cell types into blood vessel organoids.
Programmatic introduction of parenchymal cell types into blood vessel organoids.
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DOI：
10.1016/j.stemcr.2021.08.014
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发表时间：
2021-10-12
影响因子：
5.9
通讯作者：
Mali P
中科院分区：
文献类型：
--
作者：
Dailamy A;Parekh U;Katrekar D;Kumar A;McDonald D;Moreno A;Bagheri P;Ng TN;Mali P
多能干细胞衍生的类器官改变了我们重建复杂的人体组织三维模型的能力。然而，用于创建它们的定向分化方法不具备引入跨胚层细胞类型的能力。在这里，我们提出了一种自下而上的工程方法，通过将遗传重编程与化学指导的类器官分化相结合来构建血管化的人体组织。作为概念证明，我们通过血管类器官中转录因子的过度表达创建了神经血管和肌肉血管类器官。我们从标记基因表达和组成方面全面描述了神经血管类器官的特征，并证明这些类器官在培养物中可维持神经和血管功能至少 45 天。最后，我们证明了肌血管类器官聚集体的慢性电刺激是从类器官工程化成熟和大规模血管化骨骼肌组织的潜在途径。我们的方法提供了构建完全源自多能干细胞的任何类型的多样化血管化组织的路线图。通过血管类器官中的基因重编程构建的神经和肌肉血管组织 神经血管类器官在体外可持续至少 45 天 神经血管类器官证明功能性神经和血管细胞 慢性电刺激可以驱动肌血管类器官成熟 用跨胚层细胞类型构建血管化组织是类器官工程中的主要挑战。在这里，作者利用遗传重编程与标准化学定向分化相结合来生成谱系特异性的血管化类器官。通过在类器官分化过程中表达谱系特异性转录因子，他们展示了一种完全由多能干细胞生成肌血管和神经血管组织的强大方案。
Pluripotent stem cell-derived organoids have transformed our ability to recreate complex three-dimensional models of human tissue. However, the directed differentiation methods used to create them do not afford the ability to introduce cross-germ-layer cell types. Here, we present a bottom-up engineering approach to building vascularized human tissue by combining genetic reprogramming with chemically directed organoid differentiation. As a proof of concept, we created neuro-vascular and myo-vascular organoids via transcription factor overexpression in vascular organoids. We comprehensively characterized neuro-vascular organoids in terms of marker gene expression and composition, and demonstrated that the organoids maintain neural and vascular function for at least 45 days in culture. Finally, we demonstrated chronic electrical stimulation of myo-vascular organoid aggregates as a potential path toward engineering mature and large-scale vascularized skeletal muscle tissue from organoids. Our approach offers a roadmap to build diverse vascularized tissues of any type derived entirely from pluripotent stem cells. Neuro- and myo-vascular tissue built via genetic reprogramming in vascular organoids Neuro-vascular organoids were sustained in vitro for at least 45 days Neuro-vascular organoids demonstrated functional neural and vascular cells Myo-vascular organoid maturation could be driven by chronic electrical stimulation Building vascularized tissue with cross-germ-layer cell types is a major challenge in organoid engineering. Here, the authors leverage genetic reprogramming in conjunction with standard chemically directed differentiation to generate lineage-specific vascularized organoids. By expressing lineage-specifying transcription factors during organoid differentiation, they demonstrate a robust protocol for generating myo-vascular and neuro-vascular tissues entirely from pluripotent stem cells.
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DOI：
10.1126/science.aaw7567
发表时间：
2019-06-07
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Takebe T;Wells JM
通讯作者：
Wells JM
影响因子：
64.8
作者：
Qian H;Kang X;Hu J;Zhang D;Liang Z;Meng F;Zhang X;Xue Y;Maimon R;Dowdy SF;Devaraj NK;Zhou Z;Mobley WC;Cleveland DW;Fu XD
通讯作者：
Fu XD
影响因子：
23.9
作者：
Low, Jian Hui;Li, Pin;Xia, Yun
通讯作者：
Xia, Yun
DOI：
10.1073/pnas.1008322108
发表时间：
2011-01-25
影响因子：
11.1
作者：
Yusa, Kosuke;Zhou, Liqin;Craig, Nancy L.
通讯作者：
Craig, Nancy L.
影响因子：
46.9
作者：
Mansour AA;Gonçalves JT;Bloyd CW;Li H;Fernandes S;Quang D;Johnston S;Parylak SL;Jin X;Gage FH
通讯作者：
Gage FH