State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
Cell Stem Cell. 2024 May 2;31(5):772-787.e11. doi: 10.1016/j.stem.2024.03.007. Epub 2024 Apr 1.
Neonatal spinal cord tissues exhibit remarkable regenerative capabilities as compared to 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 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 Tenascin (TNC) in DNSCM were identified as contributors to these abilities. Furthermore, DNSCM demonstrated superior 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.
与成年脊髓组织相比，新生儿脊髓组织在损伤后具有显著的再生能力，但细胞外基质 (ECM) 在这一过程中的作用仍不清楚。在这里，我们发现与成年脊髓相比，早期发育的脊髓具有更高水平的与神经发育和轴突生长相关的 ECM 蛋白，但抑制性蛋白聚糖较少。从新生 (DNSCM) 和成年 (DASCM) 兔去细胞化的脊髓 ECM 保留了这些差异。DNSCM 比 DASCM 更有效地促进神经祖细胞 (NPCs) 的增殖、迁移和神经元分化，并促进脊髓类器官的轴突生长和再生。DNSCM 中的多效蛋白 (PTN) 和腱生蛋白 (TNC) 被确定为这些能力的贡献者。此外，DNSCM 在脊髓损伤 (SCI) 模型中作为 NPC 和类器官的递送载体表现出优异的性能。这表明来自早期发育阶段的 ECM 线索可能对脊髓的显著再生能力有重要贡献。
