BDNF-producing human mesenchymal stem cells in an alginate-matrix: neuroprotection and cochlear implant coating stability in vitro

Objective:

The cochlear implant (CI) outcome might be improved, amongst others, by protection of spiral ganglion neurons (SGN) through a chronical application of neurotrophic factors like BDNF (brain-derived neurotrophic factor). Genetically modified cells, encapsulated in alginate to avoid migration or rejection, implanted as a CI-coating, may be a feasible drug delivery system.

Methods:

Bone marrow-derived human mesenchymal stem cells (MSCs) were expanded, genetically modified for BDNF-production and encapsulated in alginate. To study the neuroprotective effect, beads were formed of the alginate-MSC-matrix and co-cultivated for 48h with dissociated SGN. The bead stability was macroscopically verified and the BDNF-amount in the pooled supernatant was analyzed by ELISA-detection. The survival rate of the SGN is evaluated after fixation and neuron-specific immunocytochemistry.

By dip coating the matrix is linked to CI-electrode models. The stability of this coating is tested by repeated insertion of the CI-electrode models in an artificial cochlea model followed by microscopic control for abrasion.

Results:

The formed beads are stable in culture, BDNF is produced (pg-range) and the SGN are significantly protected against degeneration. By dip coating the matrix is linkable to the CI-electrode and the degree of abrasion is low after first insertion but increased by multiple repetitions.

Conclusions:

Alginate-encapsulated, BDNF-producing MSCs coated on CI-electrodes are a promising system for chronical drug delivery. Further investigations have to concentrate on lifespan and maintenance of BDNF-production of the MSCs and an automation of the coating-process.

Publication History

Publication Date:
18 April 2018 (online)