近日，首尔国立大学的In-Bo Han和Byung-Soo Kim团队报告了离子处理的hMSCs中制备了氧化铁纳米颗粒(IONP)结合外泌体模拟纳米囊泡(NV-IONP)，并在脊髓损伤的临床相关模型中评估其治疗效果。与由未经处理的hMSCs制备的外泌体模拟纳米囊泡(NV)相比，NV- ionp不仅含有可作为磁导导航工具的离子，而且还携带更多可被输送到靶细胞的治疗性生长因子。NV-IONP内治疗性生长因子数量的增加归因于离子缓慢电离为铁离子，铁离子激活hMSCs中JNK和c-Jun信号级联。体内在磁引导下全身注射NV-IONP可显著增加损伤脊髓内NV-IONP的累积量。累积的NV-IONP增强了损伤脊髓的血管形成，减轻了炎症和细胞凋亡，从而改善了脊髓功能。综上所述，这些发现突出了治疗效果增强的细胞外纳米囊泡的发展，并证明了它们修复损伤脊髓的可行性。
The complexity of pathology in spinal cord injury (SCI), including axonal loss, inflammation, glial scar formation, and blood vessel disruption, suggests that mono-therapy may be inadequate for the treatment of SCI. Recently, hMSC therapy has been suggested as a favored approach for the treatment of SCI, as hMSCs can secrete multifactorial therapeutic factors for neuroprotection, angiogenesis, and immunomodulation. However, the direct implantation of hMSCs to an injured spinal cord is significantly invasive as compared to systemic administration, and thus it limits clinical translation for the treatment of SCI. Moreover, implanted hMSCs show poor survival rate, and hMSCs do not differentiate into neurons in injured spinal cord. These issues suggest that hMSC-exosomes may be an adequate therapeutic agent for the treatment of SCI. As various therapeutic growth factors and their mRNAs are present in hMSC-exosomes, they have an outstanding ability to repair tissue as compared to exosomes derived from other cell types such as fibroblasts. Additionally, several recent studies reported that hMSC-exosomes also show therapeutic effects for central nervous system (CNS) diseases including SCI. Although hMSC-exosome therapy has advantages over hMSC therapy, hMSC-exosome technology should be further improved for clinical application. hMSCs form only a small amount of exosomes (1–4 µg exosome proteins from 106 cells per day). Therefore, longterm cell culture and large number of hMSCs are required to produce sufficient amount of hMSC-exosomes for clinical applications. However, the MSCs at the late passage exhibit significantly reduced gene and protein expression of growth factors, which would reduce the quantity of therapeutic growth factors and their mRNAs in the secreted exosomes. Therefore in this study, they utilized exosome-mimetic nanovesicles derived from hMSCs for treatment of SCI.
Recently, Professor In-Bo Han and Professor Byung-Soo Kim from Seoul National University fabricated iron oxide nanoparticle (IONP)–incorporated exosome-mimetic nanovesicles (NV-IONP) from IONP-treated hMSCs, and evaluated their therapeutic efficacy in a clinically relevant model for spinal cord injury. Compared to exosome-mimetic nanovesicles (NV) prepared from untreated hMSCs, NV-IONP not only contained IONPs which act as a magnet-guided navigation tool but also carried greater amounts of therapeutic growth factors that can be delivered to the target cells. The increased amounts of therapeutic growth factors inside NV-IONP were attributed to IONPs that are slowly ionized to iron ions which activate the JNK and c-Jun signaling cascades in hMSCs. In vivo systemic injection of NV-IONP with magnetic guidance significantly increased the amount of NV-IONP accumulating in the injured spinal cord. Accumulated NV-IONP enhanced blood vessel formation, attenuated inflammation and apoptosis in the injured spinal cord, and consequently improved spinal cord function. Taken together, these findings highlight the development of therapeutic efficacy-potentiated extracellular nanovesicles and demonstrate their feasibility for repairing injured spinal cord.