Department of Obstetrics, University Hospital of Zurich, Zurich, Switzerland.
Institute for Biomechanics, Eidgenössische Technische Hochschule (ETH) Zurich, Zurich, Switzerland.
EMBO Rep. 2018 Aug;19(8). doi: 10.15252/embr.201845964. Epub 2018 Jul 2.
The fate of mesenchymal stem cells (MSCs) in the perivascular niche, as well as factors controlling their fate, is poorly understood. Here, we study MSCs in the perivascular microenvironment of endothelial capillaries by modifying a synthetic 3D biomimetic poly(ethylene glycol) (PEG)-hydrogel system We show that MSCs together with endothelial cells form micro-capillary networks specifically in soft PEG hydrogels. Transcriptome analysis of human MSCs isolated from engineered capillaries shows a prominent switch in extracellular matrix (ECM) production. We demonstrate that the ECM phenotypic switch of MSCs can be recapitulated in the absence of endothelial cells by functionalizing PEG hydrogels with the Notch-activator Jagged1. Moreover, transient culture of MSCs in Notch-inducing microenvironments reveals the reversibility of this ECM switch. These findings provide insight into the perivascular commitment of MSCs by use of engineered niche-mimicking synthetic hydrogels.
血管周隙间间充质干细胞（MSCs）的命运，以及控制其命运的因素，目前还知之甚少。在这里，我们通过修改一种合成的 3D 仿生聚乙二醇（PEG）水凝胶系统来研究血管周隙内皮毛细血管中的 MSC。我们发现 MSC 与内皮细胞一起在软 PEG 水凝胶中形成微毛细血管网络。从工程化毛细血管中分离出的人 MSC 的转录组分析显示细胞外基质（ECM）的产生明显发生了转变。我们证明，通过将 Notch 激活剂 Jagged1 功能化 PEG 水凝胶，可以在没有内皮细胞的情况下再现 MSC 的 ECM 表型转变。此外，MSC 在 Notch 诱导的微环境中的短暂培养揭示了这种 ECM 转变的可逆性。这些发现通过使用工程化的龛样仿生合成水凝胶为 MSC 的血管周隙分化提供了深入的了解。
