Encapsulated cell device approach for combined electrical stimulation and neurotrophic treatment of the deaf cochlea

Konerding, Wiebke; Janßen, Hilke Catherina; Hubka, Peter; Tornøe, Jens; Mistrík, Pavel; Wahlberg, Lars U.; Lenarz, Thomas; Kral, Andrej; Scheper, Verena

doi:10.1016/j.heares.2017.04.013

Cited by 23 publications

(19 citation statements)

References 70 publications

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“…The studies showed that the surgery was safe and well tolerated by the patients. Konerding et al, [28] recently studied the combined effect of repeated long-term electrical stimulation (suggested to reduce SGN degeneration) and an implanted GDNF-releasing EC device on the inner ear. The effect on electrical responsiveness of the auditory system was relatively weak, and the preservation of SGNs was only evident in animals that were also subjected to electrical stimulation.…”

Section: Resultsmentioning

confidence: 99%

The feasibility of an encapsulated cell approach in an animal deafness model

Fransson

Tornøe

Wahlberg

et al. 2018

Journal of Controlled Release

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For patients with profound hearing loss a cochlear implant (CI) is the only treatment today. The function of a CI depends in part of the function and survival of the remaining spiral ganglion neurons (SGN). It is well known from animal models that inner ear infusion of neurotrophic factors prevents SGN degeneration and maintains electrical responsiveness in deafened animals. The purpose with this study was to investigate the effects of a novel encapsulated cell (EC) device releasing neurotrophic factors in the deafened guinea pig.The results showed that an EC device releasing glial cell line-derived neurotrophic factor (GDNF) or brain-derived neurotrophic factor (BDNF) implanted for four weeks in deafened guinea pigs significantly preserved the SGNs and maintained their electrical responsiveness. There was a significant difference between BDNF and GDNF in favour of GDNF. This study, demonstrating positive structural and functional effects in the deafened inner ear, suggests that an implanted EC device releasing biologically protective substances offers a feasible approach for treating progressive hearing impairment.

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Section: Resultsmentioning

confidence: 99%

The feasibility of an encapsulated cell approach in an animal deafness model

Fransson

Tornøe

Wahlberg

et al. 2018

Journal of Controlled Release

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“…(iii) Coating the electrode carrier with cells producing therapeutic molecules. The advantage of this approach is to be a source of complex macromolecules (56)(57)(58)(59)(60). However, stem cells are limited to the production of bioactive substances that are naturally produced in the body.…”

Section: Discussionmentioning

confidence: 99%

Long-Term in vivo Release Profile of Dexamethasone-Loaded Silicone Rods Implanted Into the Cochlea of Guinea Pigs

et al. 2020

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“…To enhance the therapeutic effect achievable with MSCs we here developed a lentivirally based system for BDNF‐overexpression and secretion by human mesenchymal stem cells (hMSCs). The transplantation of BDNF‐overexpressing hMSCs should be linked to a delivery system avoiding cell migration and allowing nutrition and growth factor diffusion such as encapsulated cell devices (Konerding et al, ; Wahlberg et al, ) or hydrogel entrapment (Hütten et al, ). For this purpose, it may be beneficial to differentiate the hMSC into chondrocytes: firstly, differentiated cells are less carcinogenic or tumorigenic, and secondly, chondrocytes are able to withstand hypoxic conditions and low nutrient supply.…”

Section: Introductionmentioning

confidence: 99%

BDNF‐overexpressing human mesenchymal stem cells mediate increased neuronal protection in vitro

Scheper

Schwieger

Hamm

et al. 2019

J of Neuroscience Research

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The use of neurotrophic factors as therapeutic agents for neurodegenerative diseases is considered as an approach aimed at restoring and maintaining neuronal function in the peripheral and central nervous system. Since the neuroprotective effect is depending on chronic delivery of the neurotrophic factors a sustained application, e.g., via cell‐based delivery is necessary. Human mesenchymal stem cells (hMSCs) were lentivirally modified to overexpress brain‐derived neurotrophic factor (BDNF) and to express fluorescent marker genes for easy visualization. Since genetically modified cells should be site‐specifically retained (e.g., by encapsulation) in the patients to avoid adverse effects the cells were additionally differentiated to chondrocytes to hypothetically improve their vitality and survival in a delivery matrix. Different polycations for lentiviral transduction were investigated for their efficiency. The success of differentiation was determined by analysis of chondrocyte marker genes and the neuroprotective effect of BDNF‐overexpressing cells was exemplarily investigated on neurons of the peripheral auditory system. The genetically modified hMSCs overexpressed BDNF from under 1 to 125 ng ml−1 day−1 depending on the donor and transfection method. Using protamine sulfate the transfection efficacy was superior compared to the use of polybrene. The BDNF secreted by the MSCs was significantly neuroprotective in comparison to the relevant controls even though the produced mean concentrations were lower than the effective concentrations for recombinant industrially produced proteins described in literature. The presented system of BDNF‐overexpressing hMSCs is neuroprotective and is therefore considered as a promising method for sustained delivery of proteins in therapeutically relevant amounts to degenerating neuronal structures.

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Encapsulated cell device approach for combined electrical stimulation and neurotrophic treatment of the deaf cochlea

Cited by 23 publications

References 70 publications

The feasibility of an encapsulated cell approach in an animal deafness model

The feasibility of an encapsulated cell approach in an animal deafness model

Long-Term in vivo Release Profile of Dexamethasone-Loaded Silicone Rods Implanted Into the Cochlea of Guinea Pigs

BDNF‐overexpressing human mesenchymal stem cells mediate increased neuronal protection in vitro

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