Extracellular Vesicles as a New Cell-Based but Cell-Free Delivery System for BDNF

Introduction Mesenchymal stem cells (MSCs) are already being used for regenerative cell therapies in a variety of medical areas. Nowadays, the research focuses on the paracrine effects of the cells. Extracellular vesicles (EVs) that are secreted by virtually every cell type and contain a specific combination of bioactive molecules (proteins, enzymes, growth factors, cytokines, as well as lipids and RNA) have gained in importance. Numerous in vitro and in vivo studies show that neurotrophins protect the cells of the inner ear from degeneration.

Method EVs were isolated from human bone marrow and umbilical cord MSCs, and spiral ganglion neuron (SGN) from neonatal (P3-5) Sprague Dawley rats. The SGN were cultured with different EVs in different concentrations and combinations (with and without exogenous BDNF). After 48 hours of culture, the SGNs were fixed, stained and neuronal survival rate, neurite length and morphology were determined. In addition, the concentration of BDNF in EVs (varying production) was determined.

Results Survival rates and neurite length of SGN were significantly increased by the treatment with EVs. Furthermore, the percentage of bipolar neurons was increased. In addition, we showed that EVs contain different amounts of BDNF after the manufacturing process, so their protective effect on the SGN varies. By combining inactive EVs (minimal amount of BDNF) with BDNF, the survival rate of the SGN is increased and the protection level of the active EVs can be reached.

Conclusion The application of EVs is a promising therapeutic approach for enhancement of the cochlear environment.

Publication History

Article published online:
10 June 2020