Kim Jong-Tae, Han Sung Woo, Youn Dong Hyuk, Jung Harry, Lee Eun-Ho, Kang Sung-Min, Cho Yong-Jun, Jeon Jin Pyeong
Institute of New Frontier Research, Hallym University College of Medicine, Chuncheon 24252, Republic of Korea.
Department of Green Chemical Engineering, Sangmyung University, Cheonan 31066, Republic of Korea.
APL Bioeng. 2025 Apr 1;9(2):026101. doi: 10.1063/5.0244057. eCollection 2025 Jun.
One of the major obstacles to neural recovery following intracerebral hemorrhage (ICH) is the cavity-like lesion that occurs at the site of the hemorrhage, which impedes axonal regeneration. Here, we aim to address this challenge by investigating the migratory mechanisms of neural stem cells (NSCs) within the cavity using a hydrogel and endothelial cells. Mouse NSCs (mNSCs) isolated from the subventricular and subgranular zones using the 3D hydrogel culture were evaluated for their neurogenic, extracellular matrix (ECM), and adhesion-related mRNA expression compared to microglia (BV2) and secretory factors of human umbilical vein endothelial cells (HUVECs) and in conditions. A hydrogel mesh combining mNSCs and HUVECs was developed for its therapeutic potential. mNSCs exhibit high stemness, neurogenesis, and ECM remodeling capabilities. mNSCs demonstrated close interaction with HUVECs and the surrounding vascular structures in and studies. Furthermore, mNSCs could degrade high concentrations of fibrin to facilitate migration and adhesion. mNSCs and HUVECs formed mesh networks through cell-cell contacts and maintained the structure through Matrigel support, potentially ensuring sufficient survival and regeneration capabilities. Our proposed hydrogel mesh platform with mNSCs and HUVECs demonstrated successful maintenance of cell survival and provision of structural support for the delivered cells by promoting ECM remodeling and neurogenesis, which may aid in axonal regeneration in the cavity lesions following ICH.
脑出血（ICH）后神经恢复的主要障碍之一是出血部位出现的空洞样病变，这会阻碍轴突再生。在此，我们旨在通过使用水凝胶和内皮细胞研究空洞内神经干细胞（NSCs）的迁移机制来应对这一挑战。使用3D水凝胶培养从脑室下区和颗粒下区分离的小鼠神经干细胞（mNSCs），与小胶质细胞（BV2）以及人脐静脉内皮细胞（HUVECs）的分泌因子相比，在特定条件下评估其神经发生、细胞外基质（ECM）和黏附相关mRNA的表达。开发了一种结合mNSCs和HUVECs的水凝胶网，并评估其治疗潜力。mNSCs表现出高干性、神经发生和ECM重塑能力。在体外和体内研究中，mNSCs与HUVECs及周围血管结构表现出密切相互作用。此外，mNSCs可以降解高浓度的纤维蛋白以促进迁移和黏附。mNSCs和HUVECs通过细胞间接触形成网状网络，并通过基质胶支持维持结构，这可能确保足够的存活和再生能力。我们提出的含有mNSCs和HUVECs的水凝胶网平台通过促进ECM重塑和神经发生，成功维持了细胞存活并为递送的细胞提供了结构支持，这可能有助于ICH后空洞病变中的轴突再生。
