Department of Anatomy and Embryology, Leiden University Medical Centre, 2333ZA Leiden, the Netherlands.
Department of Anatomy and Embryology, Leiden University Medical Centre, 2333ZA Leiden, the Netherlands; Department of Clinical Genetics, Leiden University Medical Centre, 2333ZA Leiden, the Netherlands.
Stem Cell Reports. 2024 Jul 9;19(7):946-956. doi: 10.1016/j.stemcr.2024.05.006. Epub 2024 Jun 13.
Functionality of the blood-brain barrier (BBB) relies on the interaction between endothelial cells (ECs), pericytes, and astrocytes to regulate molecule transport within the central nervous system. Most experimental models for the BBB rely on freshly isolated primary brain cells. Here, we explored human induced pluripotent stem cells (hiPSCs) as a cellular source for astrocytes in a 3D vessel-on-chip (VoC) model. Self-organized microvascular networks were formed by combining hiPSC-derived ECs, human brain vascular pericytes, and hiPSC-derived astrocytes within a fibrin hydrogel. The hiPSC-ECs and pericytes showed close interactions, but, somewhat unexpectedly, addition of astrocytes disrupted microvascular network formation. However, continuous fluid perfusion or activation of cyclic AMP (cAMP) signaling rescued the vascular organization and decreased vascular permeability. Nevertheless, astrocytes did not affect the expression of proteins related to junction formation, transport, or extracellular matrix, indicating that, despite other claims, hiPSC-derived ECs do not entirely acquire a BBB-like identity in the 3D VoC model.
血脑屏障（BBB）的功能依赖于内皮细胞（ECs）、周细胞和星形胶质细胞之间的相互作用，以调节中枢神经系统内的分子运输。大多数 BBB 的实验模型依赖于新鲜分离的原代脑细胞。在这里，我们探索了人诱导多能干细胞（hiPSCs）作为星形胶质细胞在 3D 血管芯片（VoC）模型中的细胞来源。通过在纤维蛋白水凝胶中组合 hiPSC 衍生的 ECs、人脑血管周细胞和 hiPSC 衍生的星形胶质细胞，自组织形成微血管网络。hiPSC-ECs 和周细胞表现出紧密的相互作用，但出人意料的是，星形胶质细胞的加入破坏了微血管网络的形成。然而，连续的流体灌注或环磷酸腺苷（cAMP）信号的激活挽救了血管组织并降低了血管通透性。尽管如此，星形胶质细胞并不影响与连接形成、运输或细胞外基质相关的蛋白的表达，这表明，尽管有其他说法，hiPSC 衍生的 ECs 在 3D VoC 模型中并没有完全获得类似于 BBB 的身份。
