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Adipose Stem Cell Derived Extracellular Vesicles Enhance Proliferation Of Schwann Cells Following Internalization Via Endocytosis-related Mechanism.
Maximilian Härtinger, BSc., Tamara Weiss, PhD, Anda Mann, BSc., Victoria Brandel, MSc., Flavia Millesi, BSc., Christine Radtke, Professor, MD, MBA.
Medical University Vienna, Vienna, Austria.

PURPOSE:
Schwann cells, the glial cells of the peripheral nervous system, play an essential role in the regeneration following nerve injury. By creating an environment crucial for the regrowing axon, Schwann cells are of particular interest in regenerative strategies regarding the peripheral nervous system. Novel insights into stem cell based therapeutic approaches in regenerative medicine suggest that similar effects can be achieved by using only the isolated extracellular vesicles secreted by stem cells acting as paracrine signalosomes, thereby circumventing the drawbacks of stem cell based therapies.
METHODS:
Schwann cells were isolated from rat sciatic nerves and co-cultured with adipose stem cell derived extracellular vesicles. Intracellular localization of fluorescently labeled extracellular vesicles was confirmed via 3D image analysis of confocal laser scanning microscopy images. Additionally, this study investigated the proliferative effect of extracellular vesicles following internalization by Schwann cells. Therefore, multiple EdU-proliferation assays were performed at different time points.
RESULTS:
Live cell imaging showed internalization of fluorescently labeled extracellular vesicles within 24 hours. The intracellular localization pattern of silica beads was compared to that of extracellular vesicles in Schwann cells. Striking similarities in size and distribution of fluorescent silica beads within the Schwann cell cytoplasm indicate an internalization via endocytosis-related mechanisms. Proliferation assays revealed an up to 2.5-fold increase of Schwann cell proliferation after 72 hours of extracellular vesicle treatment, in a time- and dose-dependent manner.
CONCLUSION:
This study provides first evidence for an internalization via endocytosis-related mechanisms of adipose stem cell derived extracellular vesicles by Schwann cells, and underlines the therapeutic potential of adipose stem cell derived extracellular vesicles in regenerative medicine.


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