中国科学院遗传与发育生物学研究所赵燕南等研究人员，合作利用脊髓细胞外基质的发育动态提高脊髓类器官的再生潜力。相关论文于2024年4月1日在线发表在《细胞—干细胞》杂志上。

研究人员发现与成人脊髓相比，发育早期的脊髓具有更高水平的与神经发育，和轴突生长相关的细胞外基质（ECM）蛋白，但抑制性蛋白聚糖较少。新生兔（DNSCM）和成年兔（DASCM）的脱细胞脊髓ECM保留了这些差异。与DASCM相比，DNSCM能更有效地促进神经祖细胞（NPC）的增殖、迁移和神经元分化，并促进脊髓器官组织的轴突生长和再生。

经鉴定，DNSCM中的多效生长因子（PTN）和肌腱蛋白（TNC）是这些能力的促成因素。此外，在脊髓损伤（SCI）模型中，DNSCM作为NPC和类器官的输送载体表现出更优越的性能。这表明，早期发育阶段的ECM线索可能在很大程度上促进了脊髓的突出再生能力。

据悉，与成人脊髓组织相比，新生儿脊髓组织在损伤后表现出显著的再生能力，但ECM在这一过程中的作用却一直难以捉摸。

附：英文原文

Title: Harnessing developmental dynamics of spinal cord extracellular matrix improves regenerative potential of spinal cord organoids

Author: 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

Issue&Volume: 2024-04-01

Abstract: Neonatal spinal cord tissues exhibit remarkable regenerative capabilities as comparedto adult spinal cord tissues after injury, but the role of extracellular matrix (ECM)in this process has remained elusive. Here, we found that early developmental spinalcord had higher levels of ECM proteins associated with neural development and axongrowth, but fewer inhibitory proteoglycans, compared to those of adult spinal cord.Decellularized spinal cord ECM from neonatal (DNSCM) and adult (DASCM) rabbits preservedthese differences. DNSCM promoted proliferation, migration, and neuronal differentiationof neural progenitor cells (NPCs) and facilitated axonal outgrowth and regenerationof spinal cord organoids more effectively than DASCM. Pleiotrophin (PTN) and Tenascin(TNC) in DNSCM were identified as contributors to these abilities. Furthermore, DNSCMdemonstrated superior performance as a delivery vehicle for NPCs and organoids inspinal cord injury (SCI) models. This suggests that ECM cues from early developmentstages might significantly contribute to the prominent regeneration ability in spinalcord.

DOI: 10.1016/j.stem.2024.03.007

Source: https://www.cell.com/cell-stem-cell/abstract/S1934-5909(24)00089-4