Vascular organoids recover blood flow in vivo

IF 33.1 1区生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Nature biotechnology Pub Date : 2025-07-15 DOI:10.1038/s41587-025-02747-0

Iris Marchal

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引用次数: 0

Abstract

Developing vascular organoids (VOs) that faithfully mimic human blood vessels is difficult because both endothelial and mural cells need to be co-differentiated and stably maintained in an organized structure. Existing models offer limited control over cellular composition and incomplete maturation. Now, in Cell Stem Cell, Gong et al. describe a protocol to generate functional VOs in 5 days that engraft in vivo, which provides potential clinical utility.

Building on previously developed protocols, the authors created VOs by transiently activating the transcription factors (TFs) ETV2 and NKX3.1 to enable the co-differentiation of an endothelial and a mural compartment from induced pluripotent stem cells. By expressing the TFs using chemically modified mRNA, the VOs could be produced without a genetic footprint. Although VOs did not need exogenous extracellular matrix to grow, embedding them in hydrogel led to enhanced vascular maturation that resulted in the formation of larger, structured vessels. Single-cell transcriptomics showed that VOs contained heterogeneous vascular cell populations, and changing the duration of TF activation could influence endothelial phenotypes.

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类血管器官在体内恢复血液流动

由于内皮细胞和附壁细胞都需要共分化并稳定地维持在一个有组织的结构中，因此开发真实地模拟人类血管的类血管器官（VOs）是困难的。现有的模型提供有限的控制细胞组成和不完全成熟。现在，在Cell Stem Cell中，Gong等人描述了一种在5天内产生功能性VOs并在体内移植的方案，这具有潜在的临床应用价值。在先前开发的方案的基础上，作者通过瞬时激活转录因子（tf） ETV2和NKX3.1来创建VOs，从而使内皮细胞和壁室从诱导多能干细胞中共分化。通过使用化学修饰的mRNA表达tf，可以在没有遗传足迹的情况下产生vo。虽然VOs不需要外源性细胞外基质来生长，但将它们包埋在水凝胶中可以促进血管成熟，从而形成更大、更有结构的血管。单细胞转录组学表明，VOs中含有异质性的血管细胞群，改变TF激活的持续时间可以影响内皮表型。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Nature biotechnology 工程技术-生物工程与应用微生物

CiteScore

63.00

自引率

1.70%

发文量

382

审稿时长

3 months

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