Developmentally engineered bio-assemblies releasing neurotrophic exosomes guide in situ neuroplasticity following spinal cord injury.
Developmentally engineered bio-assemblies releasing neurotrophic exosomes guide in situ neuroplasticity following spinal cord injury.
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DOI：
10.1016/j.mtbio.2022.100406
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发表时间：
2022-12
影响因子：
8.2
通讯作者：
Liu, Wenjia
中科院分区：
文献类型：
--
作者：
Yan, Jin;Zhang, Liqiang;Li, Liya;He, Wangxiao;Liu, Wenjia
新兴的组织工程生物组件正在彻底改变再生医学，并提供了一个潜在的计划来保证干细胞衍生治疗的体内预测性能，从而支持其临床转化。间充质干细胞（MSC）在治疗神经系统损伤，特别是脊髓损伤（SCI）方面显示出诱人的潜力，但未能对临床结果产生影响。在此，在胚胎发育理论的指导下，适当的细胞缩窄或聚集是形成几何和功能组织结构的关键启动子，建立了一种发育工程策略，通过包括还原剂、能量和机械力刺激的三级顺序诱导程序将DPMSCs组装成称为Spinor的生物组装体。 Spinor 表现出与脊髓组织相似的几何结构，并获得自主释放外泌体的最佳数量和质量，以抑制疤痕和炎症并促进轴突再生。作为脊髓筋膜和外泌体母体，Spinor 在体内引导脊髓的原位神经可塑性，并导致 SCI 后大鼠的运动显着改善、感觉恢复和更快的尿反射恢复，同时保持高度有利的生物安全性。总的来说，Spinor 不仅是一种潜在的临床治疗范例，作为重温 SCI 中普罗米修斯神话的活“外泌体母舰”，而且可以被视为允许开发工程制造具有复杂拓扑特征和内置生物功能属性的仿生生物组件，以实现包括神经系统在内的复杂组织的再生。
The emerging tissue-engineered bio-assemblies are revolutionizing the regenerative medicine, and provide a potential program to guarantee predictive performance of stem-cell-derived treatments in vivo and hence support their clinical translation. Mesenchymal stem cell (MSC) showed the attractive potential for the therapy of nervous system injuries, especially spinal cord injury (SCI), and yet failed to make an impact on clinical outcomes. Herein, under the guidance of the embryonic development theory that appropriate cellular coarctations or clustering are pivotal initiators for the formation of geometric and functional tissue structures, a developmentally engineered strategy was established to assemble DPMSCs into a bio-assembly termed Spinor through a three-level sequential induction programme including reductant, energy and mechanical force stimulation. Spinor exhibited similar geometric construction with spinal cord tissue and attain autonomy to released exosome with the optimized quantity and quality for suppressing cicatrization and inflammation and promoting axonal regeneration. As a spinal cord fascia and exosome mothership, Spinor guided the in-situ neuroplasticity of spinal cord in vivo, and caused the significant motor improvement, sensory recovery, and faster urinary reflex restoration in rats following SCI, while maintaining a highly favorable biosafety profile. Collectively, Spinor not only is a potentially clinical therapeutic paradigm as a living “exosome mothership” for revisiting Prometheus' Myth in SCI, but can be viewed allowing developmentally engineered manufacturing of biomimetic bio-assemblies with complex topology features and inbuilt biofunction attributes towards the regeneration of complex tissues including nervous system.
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影响因子：
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