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通过激活干细胞归巢因子靶向遗传性耳聋的内耳细胞疗法。

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

作者信息

Kamiya Kazusaku

机构信息

Department of Otorhinolaryngology, Faculty of Medicine, Juntendo University , Tokyo, Japan.

出版信息

Front Pharmacol. 2015 Jan 27;6:2. doi: 10.3389/fphar.2015.00002. eCollection 2015.

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.

摘要

先天性耳聋影响约千分之一的儿童,其中一半以上具有遗传背景,如连接蛋白26(CX26)基因突变。内耳细胞疗法治疗感音神经性听力损失有望成为遗传性耳聋的有效治疗方法。此前,我们开发了一种内耳细胞疗法的新策略,使用骨髓间充质干细胞作为补充,用于耳蜗纤维细胞进行耳蜗离子转运。对于针对遗传性耳聋的细胞疗法,需要一种更有效的细胞递送系统,以将干细胞诱导到耳蜗组织中,因为基因突变会影响所有表达如编码CX26的GJB2等基因的耳蜗细胞。干细胞归巢是激活有效细胞递送至耳蜗组织的关键机制之一。在我们的研究中,单核细胞趋化蛋白-1、基质细胞衍生因子-1及其受体被发现是干细胞募集到耳蜗组织的关键调节因子。因此,激活干细胞归巢可能是遗传性耳聋听力恢复的有效策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7ed0/4307216/9f52b88d03e5/fphar-06-00002-g0001.jpg

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