Ran Ning, Li Wenxiang, Zhang Renjie, Lin Caorui, Zhang Jianping, Wei Zhijian, Li Zonghao, Yuan Zhongze, Wang Min, Fan Baoyou, Shen Wenyuan, Li Xueying, Zhou Hengxing, Yao Xue, Kong Xiaohong, Feng Shiqing
Orthopedic Research Center of Shandong University &Advanced Medical Research Institute, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
Department of Orthopedics, Qilu Hospital of Shandong University, Jinan, Shandong, China.
Bioact Mater. 2022 Jul 22;25:766-782. doi: 10.1016/j.bioactmat.2022.07.002. eCollection 2023 Jul.
Spinal cord injury (SCI) causes motor, sensory and automatic impairment due to rarely axon regeneration. Developing effective treatment for SCI in the clinic is extremely challenging because of the restrictive axonal regenerative ability and disconnection of neural elements after injury, as well as the limited systemic drug delivery efficiency caused by blood spinal cord barrier. To develop an effective non-invasive treatment strategy for SCI in clinic, we generated an autologous plasma exosome (AP-EXO) based biological scaffold where AP-EXO was loaded with neuron targeting peptide (RVG) and growth-facilitating peptides (ILP and ISP). This scaffold can be targeted delivered to neurons in the injured area and elicit robust axon regrowth across the lesion core to the levels over 30-fold greater than naïve treatment, thus reestablish the intraspinal circuits and promote motor functional recovery after spinal cord injury in mice. More importantly, in , human plasma exosomes (HP-EXO) loaded with combinatory peptides of RVG, ILP and ISP showed safety and no liver and kidney toxicity in the application to nude SCI mice. Combining the efficacy and safety, the AP-EXO-based personalized treatment confers functional recovery after SCI and showed immense promising in biomedical applications in treating SCI. It is helpful to expand the application of combinatory peptides and human plasma derived autologous exosomes in promoting regeneration and recovery upon SCI treatment.
脊髓损伤（SCI）由于轴突再生极少，会导致运动、感觉和自主功能障碍。由于轴突再生能力受限、损伤后神经元件的连接中断，以及血脊髓屏障导致的全身药物递送效率有限，在临床上开发有效的脊髓损伤治疗方法极具挑战性。为了在临床上开发一种有效的非侵入性脊髓损伤治疗策略，我们制备了一种基于自体血浆外泌体（AP-EXO）的生物支架，其中AP-EXO负载了神经元靶向肽（RVG）和促进生长肽（ILP和ISP）。这种支架可以靶向递送至损伤区域的神经元，并引发强大的轴突再生，穿过损伤核心，再生水平比单纯治疗高出30倍以上，从而重建脊髓内回路，促进小鼠脊髓损伤后的运动功能恢复。更重要的是，负载RVG、ILP和ISP组合肽的人血浆外泌体（HP-EXO）在应用于裸鼠脊髓损伤模型时显示出安全性，且无肝肾毒性。结合疗效和安全性，基于AP-EXO的个性化治疗可使脊髓损伤后实现功能恢复，并在脊髓损伤的生物医学应用中显示出巨大的前景。这有助于扩大组合肽和人血浆来源的自体外泌体在促进脊髓损伤治疗后的再生和恢复方面的应用。
