Creatine supports propagation and promotes neuronal differentiation of inner ear progenitor cells

Di Santo, Stefano; Mina, Amir; Ducray, Angélique; Widmer, Hans Rudolf; Senn, Pascal (2014). Creatine supports propagation and promotes neuronal differentiation of inner ear progenitor cells. NeuroReport, 25(7), pp. 446-451. Lippincott Williams & Wilkins 10.1097/WNR.0000000000000112

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Long-term propagation of inner ear-derived progenitor/stem cells beyond the third generation and differentiation into inner ear cell types has been shown to be feasible, but challenging. We investigated whether the known neuroprotective guanidine compound creatine (Cr) promotes propagation of inner ear progenitor/stem cells as mitogen-expanded neurosphere cultures judged from the formation of spheres over passages. In addition, we studied whether Cr alone or in combination with brain-derived neurotrophic factor (BDNF) promotes neuronal differentiation of inner ear progenitors. For this purpose, early postnatal rat spiral ganglia, utricle, and organ of Corti-derived progenitors were grown as floating spheres in the absence (controls) or presence of Cr (5 mM) from passage 3 onward. Similarly, dissociated sphere-derived cultures were differentiated for 14 days in the presence or absence of Cr (5 mM) and spiral ganglia sphere-derived cultures in a combination of Cr with the neurotrophin BDNF (50 ng/ml). We found that the cumulative total number of spheres over all passages was significantly higher after Cr supplementation as compared with controls in all the three inner ear cultures. In contrast, sphere sizes were not affected by the administration of Cr. Administration of Cr during differentiation of spiral ganglia cells resulted in a significantly higher density of β-III-tubulin-positive cells compared with controls, whereas densities of myosin VIIa-positive cells in cultures of utricle and organ of Corti were not affected by the treatment. Importantly, a combination of Cr with the neurotrophin BDNF resulted in further significantly increased densities of β-III-tubulin-positive cells in cultures of spiral ganglia cells as compared with single treatments. In sum, Cr promoted continuing propagation of rat inner ear-derived progenitor cells and supported specifically in combination with BDNF the differentiation of neuronal cell types from spiral ganglion-derived spheres.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Neurosurgery
04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Ear, Nose and Throat Disorders (ENT)

UniBE Contributor:

Di Santo, Stefano; Mina, Amir; Widmer, Hans Rudolf and Senn, Pascal

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0959-4965

Publisher:

Lippincott Williams & Wilkins

Language:

English

Submitter:

Martin Kompis

Date Deposited:

07 Mar 2014 09:10

Last Modified:

20 Mar 2015 13:47

Publisher DOI:

10.1097/WNR.0000000000000112

PubMed ID:

24356107

Uncontrolled Keywords:

auditory neurons, cochlea, creatine, differentiation, hearing loss therapy, inner ear stem cells, propagation, spiral ganglion, utricle

URI:

https://boris.unibe.ch/id/eprint/43524

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