Abstract

Congenital deafness affects about 1 in 1000 children and more than half of them have a genetic background such as Connexin26 (CX26) gene mutation. Inner ear cell therapy for sensorineural hearing loss has been expected to be an effective therapy for hereditary deafness. Previously, we developed a novel strategy for inner ear cell therapy using bone marrow mesenchymal stem cells as a supplement for cochlear fibrocytes functioning for cochlear ion transport. For cell therapy targeting hereditary deafness, a more effective cell delivery system to induce the stem cells into cochlear tissue is required, because gene mutations affect all cochlear cells cochlear cells expressing genes such as GJB2 encoding CX26. Stem cell homing is one of the crucial mechanisms to be activated for efficient cell delivery to the cochlear tissue. In our study, monocyte chemotactic protein-1, stromal cell-derived factor-1 and their receptors were found to be a key regulator for stem cell recruitment to the cochlear tissue. Thus, the activation of stem cell homing may be an efficient strategy for hearing recovery in hereditary deafness.

Highlights

  • Congenital deafness affects about 1 in 1000 children and more than half of them have a genetic background such as Connexin26 (CX26) gene mutation

  • HEREDITARY DEAFNESS AND THE MOUSE MODELS ASSOCIATED WITH IONIC HOMEOSTASIS IN COCHLEA Approximately one in 1,000 children is affected by severe hearing loss at birth or during early childhood, which is defined as pre-lingual deafness (Morton, 1991; Petersen and Willems, 2006) with about half of the cases attributable to genetic causes (Birkenhager et al, 2010)

  • INNER EAR CELL THERAPY TARGETING COCHLEAR FIBROCYTE Previously, we demonstrated that local inflammation at the lateral wall promotes the invasion of transplanted mesenchymal stem cells (MSCs) to the lateral wall (Kamiya et al, 2007)

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Summary

Introduction

Congenital deafness affects about 1 in 1000 children and more than half of them have a genetic background such as Connexin26 (CX26) gene mutation. A mouse model with a mutation in BSND, which encodes barttin, shows Bartter syndrome type IV, a hearing impairment (Nomura et al, 2013) thought to be caused by a low EP.

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