Peng Wei, Xie Yong, Liu Yudong, Xu Jiaqi, Yuan Feifei, Li Chengjun, Qin Tian, Lu Hongbin, Duan Chunyue, Hu Jianzhong
Department of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Changsha, China; Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, China; Hunan Engineering Research Center of Sports and Health, Changsha, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China; Department of Spine Surgery, Wuxi 9th Affiliated Hospital of Soochow University, Wuxi, China.
Department of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Changsha, China; Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, China; Hunan Engineering Research Center of Sports and Health, Changsha, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
J Control Release. 2023 Sep;361:750-765. doi: 10.1016/j.jconrel.2023.08.025. Epub 2023 Aug 22.
Targeted delivery of small extracellular vesicles (sEVs) with low immunogenicity and fewer undesirable side effects are needed for spinal cord injury (SCI) therapy. Here, we show that RGD (Arg-Gly-Asp) peptide-decorated CD163 macrophage-derived sEVs can deliver TGF-β to the neovascular endothelial cells of the injured site and improve neurological function after SCI. CD163 macrophages are M2 macrophages that express TGF-β and are reported to promote angiogenesis and vascular stabilization in various diseases. Enriched TGF-β EVs were crucial in angiogenesis and tissue repair. However, TGF-β also boosts the formation of fibrous or glial scars, detrimental to neurological recovery. Our results found RGD-modified CD163 sEVs accumulated in the injured region and were taken up by neovascular endothelial cells. Furthermore, RGD-CD163 sEVs promoted vascular regeneration and stabilization in vitro and in vivo, resulting in substantial functional recovery post-SCI. These data suggest that RGD-CD163 sEVs may be a potential strategy for treating SCI.
脊髓损伤（SCI）治疗需要靶向递送具有低免疫原性和较少不良副作用的小细胞外囊泡（sEVs）。在此，我们表明，用RGD（精氨酸-甘氨酸-天冬氨酸）肽修饰的CD163巨噬细胞衍生的sEVs可以将TGF-β递送至损伤部位的新生血管内皮细胞，并改善SCI后的神经功能。CD163巨噬细胞是表达TGF-β的M2巨噬细胞，据报道在各种疾病中可促进血管生成和血管稳定。富含TGF-β的细胞外囊泡在血管生成和组织修复中至关重要。然而，TGF-β也会促进纤维性或胶质瘢痕的形成，对神经恢复有害。我们的结果发现，RGD修饰的CD163 sEVs在损伤区域积聚并被新生血管内皮细胞摄取。此外，RGD-CD163 sEVs在体外和体内均促进血管再生和稳定，导致SCI后功能大幅恢复。这些数据表明，RGD-CD163 sEVs可能是治疗SCI的一种潜在策略。
