Shou Jianyong, Zheng J Lisa, Gao Wei Qiang
Department of Molecular Oncology, Genentech, Inc., South San Francisco, CA 94080, USA.
Mol Cell Neurosci. 2003 Jun;23(2):169-79. doi: 10.1016/s1044-7431(03)00066-6.
Although hair cells regenerate spontaneously in birds and lower vertebrates following injury, there is yet no effective way to stimulate hair cell regeneration in mature mammalian inner ears. Here we report that a large number of hair cells are produced in the sensory epithelium of cultured adult rat utricular maculae, via adenovirus-mediated overexpression of Hath1, a human atonal homolog. The generation of new hair cells via Hath1 expression does not involve cell proliferation based on bromodeoxyuridine immunocytochemistry. Furthermore, using a similar approach, hair cells are regenerated following aminoglycoside injury in these cultures. These data show conclusively that mature mammalian inner ears have the competence to produce a large number of new hair cells. Local adenoviral gene therapy in the inner ear may be a potential approach to treatment of hearing and balance disorders.
尽管鸟类和低等脊椎动物的毛细胞在受伤后能自发再生，但目前仍没有有效的方法来刺激成熟哺乳动物内耳中的毛细胞再生。在此我们报告，通过腺病毒介导人类无调性同源基因Hath1在成年大鼠培养椭圆囊斑感觉上皮中的过表达，可产生大量毛细胞。基于溴脱氧尿苷免疫细胞化学分析，通过Hath1表达产生新毛细胞的过程不涉及细胞增殖。此外，采用类似方法，在这些培养物中，氨基糖苷损伤后也可再生毛细胞。这些数据确凿地表明，成熟哺乳动物内耳具备产生大量新毛细胞的能力。内耳局部腺病毒基因治疗可能是治疗听力和平衡障碍的一种潜在方法。
