Xue Weiwei, Li Bo, Liu Huihui, Xiao Yujie, Li Bo, Ren Lei, Li Huijuan, Shao Zhicheng
Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Institute of Pediatrics, National Children's Medical Center, Children's Hospital, Fudan University, Shanghai 200032, China.
Key Laboratory of Biomedical Engineering of Fujian Province University/Research Center of Biomedical Engineering of Xiamen, Department of Biomaterials, College of Materials, Xiamen University, Xiamen 361005, China.
iScience. 2022 Dec 26;26(1):105898. doi: 10.1016/j.isci.2022.105898. eCollection 2023 Jan 20.
The spinal cord possesses highly complex, finely organized cytoarchitecture guided by two dorsoventral morphogenic organizing centers. Thus, generation of human spinal cord tissue is challenging. Here, we demonstrated a novel method for generation of human dorsoventral spinal cord organoids using composite scaffolds. Specifically, the spinal cord ventralizing signaling Shh agonist (SAG) was loaded into a porous chitosan microsphere (PCSM), then thermosensitive Matrigel was coated on the surface to form composite microspheres with functional sustained-release SAG, termed as PCSM-Matrigel@SAG. Using PCSM-Matrigel@SAG as the core to induce 3D engineering of human spinal cord organoids from human pluripotent stem cells (ehSC-organoids), we found ehSC-organoids could form dorsoventral spinal cord-like cytoarchitecture with major domain-specific progenitors and neurons. Besides, these ehSC-organoids also showed functional calcium activity. In summary, these ehSC-organoids are of great significance for modeling spinal cord development, drug screening as 3D models for motor neuron diseases, and spinal cord injury repair.
脊髓拥有由两个背腹侧形态发生组织中心引导的高度复杂、组织精细的细胞结构。因此，生成人类脊髓组织具有挑战性。在此，我们展示了一种使用复合支架生成人类背腹侧脊髓类器官的新方法。具体而言，将脊髓腹侧化信号通路的Shh激动剂（SAG）加载到多孔壳聚糖微球（PCSM）中，然后在表面包被热敏性基质胶以形成具有功能性缓释SAG的复合微球，称为PCSM-基质胶@SAG。以PCSM-基质胶@SAG为核心，从人多能干细胞诱导生成人类脊髓类器官的三维工程（ehSC-类器官），我们发现ehSC-类器官可以形成具有主要区域特异性祖细胞和神经元的背腹侧脊髓样细胞结构。此外，这些ehSC-类器官还表现出功能性钙活性。总之，这些ehSC-类器官对于模拟脊髓发育、作为运动神经元疾病的三维模型进行药物筛选以及脊髓损伤修复具有重要意义。
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