Harnessing Developmental Dynamics of Spinal Cord Extracellular Matrix Improves Regenerative Potential of Spinal Cord Organoids
    作者: Zheng Sun, Zhenni Chen, Man Yin, Xianming Wu, Bo Guo, Xiaokang Cheng, Rui Quan, Yuting Sun, Qi Zhang, Yongheng Fan, Chen Jin, Yanyun Yin, Xianglin Hou, Weiyuan Liu, Muya Shu, Xiaoyu Xue, Ya Shi, Bing Chen, Zhifeng Xiao, Jianwu Dai, Yannan Zhao
    刊物名称: Cell Stem Cell
    Neonatal spinal cord tissues exhibit remarkable regenerative capabilities as compared to adult spinal cord tis-sues after injury, but the role of extracellular matrix (ECM) in this process has remained elusive. Here, we found that early developmental spinal cord had higher levels of ECM proteins associated with neural development and axon growth, but fewer inhibitory proteoglycans, compared to those of adult spinal cord. Decellularized spinal cord ECM from neonatal (DNSCM) and adult (DASCM) rabbits preserved these differences. DNSCM promoted proliferation, migration, and neuronal differentiation of neural progenitor cells (NPCs) and facilitated axonal outgrowth and regeneration of spinal cord organoids more effectively than DASCM. Pleiotrophin (PTN) and Te-nascin (TNC) in DNSCM were identified as contributors to these abilities. Furthermore, DNSCM demonstrated su-perior performance as a delivery vehicle for NPCs and organoids in spinal cord injury (SCI) models. This suggests that ECM cues from early development stages might significantly contribute to the prominent regeneration ability in spinal cord.