Hsueh Yu-Huan, Chen Kuan-Po, Buddhakosai Waradee, Le Phung-Ngan, Hsiung Ying-Wu, Tu Yung-Yi, Chen Wen-Liang, Lu Huai-En, Tu Yuan-Kun
Department of Orthopedic Surgery, E-Da Hospital, I-Shou University, Kaohsiung City 824, Taiwan.
College of Engineering Bioscience, National Yang Ming Chiao Tung University, Hsinchu City 300, Taiwan.
Int J Mol Sci. 2024 Dec 31;26(1):281. doi: 10.3390/ijms26010281.
Olfactory ensheathing cell (OEC) transplantation demonstrates promising therapeutic results in neurological disorders, such as spinal cord injury. The emerging cell-free secretome therapy compensates for the limitations of cell transplantation, such as low cell survival rates. However, the therapeutic benefits of the human OEC secretome remain unclear. We harvested the secretome from human mucosal OECs and characterized its protein content, identifying 709 proteins in the human OEC secretome from three donors in two passages. Thirty-nine proteins, including neurological-related proteins, such as profilin-1, and antioxidants, such as peroxiredoxin-1 and glutathione S-transferase, were shared between the six samples. The secretome consistently demonstrated potential effects such as antioxidant activity, neuronal differentiation, and quiescence exit of neural stem cells (NSCs). The total secretome produced by OECs protects NSCs from HO-induced reactive oxygen species accumulation. During induction of neuronal differentiation, secretomes promoted neurite outgrowth, axon elongation, and expression of neuronal markers. The secretome ameliorated bone morphogenetic protein 4- and fibroblast growth factor 2-induced quiescence of NSCs. The human OEC secretome triggers NSCs to exit prime quiescence, which is related to increased phosphoribosomal protein S6 expression and RNA synthesis. The human OEC secretome has beneficial effects on NSCs and may be applied in neurological disease studies.
嗅鞘细胞（OEC）移植在诸如脊髓损伤等神经系统疾病中显示出有前景的治疗效果。新兴的无细胞分泌组疗法弥补了细胞移植的局限性，如细胞存活率低。然而，人OEC分泌组的治疗益处仍不清楚。我们从人黏膜OEC中收获了分泌组并对其蛋白质含量进行了表征，在来自两个传代的三名供体的人OEC分泌组中鉴定出709种蛋白质。六个样本之间共有39种蛋白质，包括与神经相关的蛋白质，如丝切蛋白-1，以及抗氧化剂，如过氧化物酶-1和谷胱甘肽S-转移酶。该分泌组始终表现出潜在的作用，如抗氧化活性、神经元分化以及神经干细胞（NSC）的静止退出。OEC产生的总分泌组可保护NSC免受HO诱导的活性氧积累。在神经元分化诱导过程中，分泌组促进了神经突生长、轴突伸长以及神经元标志物的表达。该分泌组改善了骨形态发生蛋白4和成纤维细胞生长因子2诱导的NSC静止状态。人OEC分泌组触发NSC退出主要静止状态，这与核糖体蛋白S6表达增加和RNA合成有关。人OEC分泌组对NSC有有益作用，可应用于神经系统疾病研究。
