Yan Jin, Zhang Liqiang, Li Liya, He Wangxiao, Liu Wenjia
National & Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China.
Institute for Stem Cell & Regenerative Medicine, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China.
Mater Today Bio. 2022 Aug 24;16:100406. doi: 10.1016/j.mtbio.2022.100406. eCollection 2022 Dec.
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 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 neuroplasticity of spinal cord , 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.
新兴的组织工程生物组件正在革新再生医学，并提供了一个潜在方案，以确保干细胞衍生治疗的可预测性能，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，尤其是脊髓损伤（SCI）方面显示出诱人的潜力，但尚未对临床结果产生影响。在此，在胚胎发育理论的指导下，即适当的细胞收缩或聚集是几何和功能组织结构形成的关键启动因素，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DPMSC组装成一种称为Spinor的生物组件。Spinor表现出与脊髓组织相似的几何结构，并能够自主释放具有优化数量和质量的外泌体，以抑制瘢痕形成和炎症并促进轴突再生。作为脊髓筋膜和外泌体母舰，Spinor引导脊髓的神经可塑性，并在SCI后的大鼠中引起显著的运动改善、感觉恢复和更快的排尿反射恢复，同时保持高度良好的生物安全性。总的来说，Spinor不仅是一种潜在的临床治疗范例，作为一种活的“外泌体母舰”，用于重温SCI中的普罗米修斯神话，而且可以被视为允许对具有复杂拓扑特征和内置生物功能属性的仿生生物组件进行发育工程制造，以促进包括神经系统在内的复杂组织的再生。
