Bertucci Taylor, Kakarla Shravani, Winkelman Max A, Lane Keith, Stevens Katherine, Lotz Steven, Grath Alexander, James Daylon, Temple Sally, Dai Guohao
Neural Stem Cell Institute, Rensselaer, New York 12144, USA.
Northeastern University, Department of Bioengineering, Boston, Massachusetts 02115, USA.
APL Bioeng. 2023 Aug 8;7(3):036107. doi: 10.1063/5.0155207. eCollection 2023 Sep.
During embryonic development, endothelial cells (ECs) undergo vasculogenesis to form a primitive plexus and assemble into networks comprised of mural cell-stabilized vessels with molecularly distinct artery and vein signatures. This organized vasculature is established prior to the initiation of blood flow and depends on a sequence of complex signaling events elucidated primarily in animal models, but less studied and understood in humans. Here, we have developed a simple vascular differentiation protocol for human pluripotent stem cells that generates ECs, pericytes, and smooth muscle cells simultaneously. When this protocol is applied in a 3D hydrogel, we demonstrate that it recapitulates the dynamic processes of early human vessel formation, including acquisition of distinct arterial and venous fates, resulting in a vasculogenesis angiogenesis model plexus (VAMP). The VAMP captures the major stages of vasculogenesis, angiogenesis, and vascular network formation and is a simple, rapid, scalable model system for studying early human vascular development .
在胚胎发育过程中，内皮细胞（ECs）经历血管生成以形成原始丛，并组装成由具有分子上不同动脉和静脉特征的壁细胞稳定血管组成的网络。这种有组织的脉管系统在血流开始之前就已建立，并且依赖于一系列主要在动物模型中阐明的复杂信号事件，但在人类中研究和了解较少。在这里，我们开发了一种用于人类多能干细胞的简单血管分化方案，该方案可同时生成内皮细胞、周细胞和平滑肌细胞。当该方案应用于三维水凝胶中时，我们证明它概括了早期人类血管形成的动态过程，包括获得不同的动脉和静脉命运，从而形成血管生成血管新生模型丛（VAMP）。VAMP捕获了血管生成、血管新生和血管网络形成的主要阶段，是用于研究早期人类血管发育的简单、快速、可扩展的模型系统。
