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.

中文翻译：

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利用脊髓细胞外基质的发育动力学提高脊髓类器官的再生潜力

与损伤后的成人脊髓组织相比，新生儿脊髓组织表现出显着的再生能力，但细胞外基质（ECM）在此过程中的作用仍然难以捉摸。在这里，我们发现，与成年脊髓相比，早期发育脊髓具有较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。新生兔 (DNSCM) 和成年兔 (DASCM) 的脱细胞脊髓 ECM 保留了这些差异。 DNSCM 比 DASCM 更有效地促进神经祖细胞 (NPC) 的增殖、迁移和神经元分化，并促进脊髓类器官的轴突生长和再生。 DNSCM 中的多效蛋白 (PTN) 和腱蛋白 (TNC) 被认为是这些能力的贡献者。此外，DNSCM 在脊髓损伤 (SCI) 模型中表现出作为 NPC 和类器官的递送工具的卓越性能。这表明早期发育阶段的 ECM 信号可能对脊髓显着的再生能力有显着贡献。