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Inner ear cell therapy targeting hereditary deafness by activation of stem cell homing factors.

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.

SUBMITTER: Kamiya K

PROVIDER: S-EPMC4307216 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Inner ear cell therapy targeting hereditary deafness by activation of stem cell homing factors.

Kamiya Kazusaku K

Frontiers in pharmacology 20150127

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 d ...[more]

PMID: 25674062

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Project description:BACKGROUND:Hearing loss is a major cause of disability worldwide, impairing communication, health, and quality of life. Emerging methods of gene therapy aim to address this morbidity, which can be employed to fix a genetic problem causing hair cell dysfunction and to promote the proliferation of supporting cells in the cochlea and their transdifferentiation into hair cells. In order to extend the applicability of gene therapy, the scientific community is focusing on discovery of additional deafness genes, identifying new genetic variants associated with hearing loss, and revealing new factors that can be manipulated in a coordinated manner to improve hair cell regeneration. Here, we addressed these challenges via genome-wide measurement and computational analysis of transcriptional profiles of mouse cochlea and vestibule sensory epithelium at embryonic day (E)16.5 and postnatal day (P)0. These time points correspond to developmental stages before and during the acquisition of mechanosensitivity, a major turning point in the ability to hear. RESULTS:We hypothesized that tissue-specific transcription factors are primarily involved in differentiation, while those associated with development are more concerned with proliferation. Therefore, we searched for enrichment of transcription factor binding motifs in genes differentially expressed between the tissues and between developmental ages of mouse sensory epithelium. By comparison with transcription factors known to alter their expression during avian hair cell regeneration, we identified 37 candidates likely to be important for regeneration. Furthermore, according to our estimates, only half of the deafness genes in human have been discovered. To help remedy the situation, we developed a machine learning classifier that utilizes the expression patterns of genes to predict how likely they are to be undiscovered deafness genes. CONCLUSIONS:We used a novel approach to highlight novel additional factors that can serve as points of intervention for enhancing hair cell regeneration. Given the similarities between mouse and human deafness, our predictions may be of value in prioritizing future research on novel human deafness genes.

Dataset Information

Inner ear cell therapy targeting hereditary deafness by activation of stem cell homing factors.

Publications

Inner ear cell therapy targeting hereditary deafness by activation of stem cell homing factors.

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