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Updated: Jun 3, 2025
Coculture of Axotomized Rat Retinal Ganglion Neurons with Olfactory Ensheathing Glia, as an In Vitro Model of Adult Axonal Regeneration
Published on: November 2, 2020
Secretome of the Olfactory Ensheathing Cells Influences the Behavior of Neural Stem Cells
Yu-Huan Hsueh1,2, Kuan-Po Chen1,2, Waradee Buddhakosai1
1Department of Orthopedic Surgery, E-Da Hospital, I-Shou University, Kaohsiung City 824, Taiwan.
Abstract:
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 H2O2-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.
Insights
Human olfactory ensheathing cell (OEC) secretome shows therapeutic potential for neurological disorders. This cell-free therapy protects neural stem cells (NSCs) and promotes neuronal differentiation, offering a promising alternative to cell transplantation.
Area of Science:
- Neuroscience
- Regenerative Medicine
- Cell Biology
Background:
- Olfactory ensheathing cell (OEC) transplantation shows promise for neurological disorders like spinal cord injury.
- Cell-free secretome therapy is an emerging alternative to cell transplantation, addressing limitations like low cell survival.
- The therapeutic potential of human OEC secretome for neurological conditions requires further investigation.
Purpose of the Study:
- To characterize the protein content of human OEC secretome.
- To evaluate the effects of human OEC secretome on neural stem cells (NSCs).
- To explore the therapeutic applications of human OEC secretome in neurological disease research.
Main Methods:
- Harvesting and characterizing secretome from human mucosal OECs.
- Protein content analysis of the secretome using mass spectrometry.
- Assessing secretome effects on NSC antioxidant activity, neuronal differentiation, and quiescence exit.
Main Results:
- Identified 709 proteins in the human OEC secretome, with 39 shared proteins including neuro-related and antioxidant factors.
- Demonstrated antioxidant activity, protecting NSCs from oxidative stress (H2O2-induced ROS).
- Promoted NSC neuronal differentiation, including neurite outgrowth and axon elongation, and facilitated exit from quiescence.
Conclusions:
- The human OEC secretome possesses beneficial properties for NSCs, including neuroprotection and enhanced differentiation.
- Secretome-induced NSC activation involves increased S6 phosphorylation and RNA synthesis.
- Human OEC secretome therapy represents a promising cell-free approach for neurological disease treatment and research.
