Abilez Oscar J, Yang Huaxiao, Guan Yuan, Shen Mengcheng, Yildirim Zehra, Zhuge Yan, Venkateshappa Ravichandra, Zhao Shane R, Gomez Angello H, El-Mokahal Marcel, Dunkenberger Logan, Ono Yoshikazu, Shibata Masafumi, Nwokoye Peter N, Tian Lei, Wilson Kitchener D, Lyall Evan H, Jia Fangjun, Wo Hung Ta, Zhou Gao, Aldana Bryan, Karakikes Ioannis, Obal Detlef, Peltz Gary, Zarins Christopher K, Wu Joseph C
Cardiovascular Institute, Stanford University, Stanford, CA, USA.
Maternal and Child Health Research Institute, Stanford University, Stanford, CA, USA.
Science. 2025 Jun 5;388(6751):eadu9375. doi: 10.1126/science.adu9375.
Although model organisms have provided insight into the earliest stages of cardiac and hepatic vascularization, we know very little about this process in humans because of ethical restrictions and the technical difficulty of obtaining embryos during very early development. In this study, we demonstrate that micropatterned human pluripotent stem cell-derived gastruloids enable in vitro modeling of the earliest stages of vascularization. We identify a combination of vascular-inducing factors that give rise to cardiac vascularized organoids with a spatially organized and branched vascular network. To show the broader utility of our vascularization strategy, we use the same vascular-inducing factors to produce hepatic vascularized organoids. Our results suggest that a conserved developmental program generates the vasculature within different types of organs.
尽管模式生物已经为心脏和肝脏血管形成的早期阶段提供了见解,但由于伦理限制以及在极早期发育阶段获取胚胎的技术难度,我们对人类的这一过程知之甚少。在本研究中,我们证明微图案化的人多能干细胞衍生类原肠胚能够对血管形成的早期阶段进行体外建模。我们确定了一组血管诱导因子的组合,这些因子能产生具有空间组织化和分支状血管网络的心脏血管化类器官。为了展示我们血管化策略更广泛的实用性,我们使用相同的血管诱导因子来生成肝脏血管化类器官。我们的结果表明,一个保守的发育程序在不同类型的器官内生成脉管系统。