کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6287492 | 1615596 | 2013 | 20 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Regeneration of mammalian cochlear and vestibular hair cells through Hes1/Hes5 modulation with siRNA
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کلمات کلیدی
PLGALipofectionthe organ of CortiscRNAqRT-PCRscrambled siRNAGFP4-HNE4-hydroxy-2-nonenal - 4-هیدروکسی-2 غیرنالSmall interfering RNA - RNA تداخل کوچکsiRNA - siRNAHair cell regeneration - بازسازی موی موsupporting cell - سلول حمایتیhair cell - سلول موNotch pathway - مسیر نچMouse - موشNanoparticle - نانوذارتquantitative real-time polymerase chain reaction - واکنش زنجیره ای پلیمراز کمی زمان واقعی استgreen fluorescent protein - پروتئین فلورسنت سبزInner ear - گوش داخلی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
سیستم های حسی
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چکیده انگلیسی
The Notch pathway is a cell signaling pathway determining initial specification and subsequent cell fate in the inner ear. Previous studies have suggested that new hair cells (HCs) can be regenerated in the inner ear by manipulating the Notch pathway. In the present study, delivery of siRNA to Hes1 and Hes5 using a transfection reagent or siRNA to Hes1 encapsulated within poly(lactide-co-glycolide acid) (PLGA) nanoparticles increased HC numbers in non-toxin treated organotypic cultures of cochleae and maculae of postnatal day 3 mouse pups. An increase in HCs was also observed in cultured cochleae and maculae of mouse pups pre-conditioned with a HC toxin (4-hydroxy-2-nonenal or neomycin) and then treated with the various siRNA formulations. Treating cochleae with siRNA to Hes1 associated with a transfection reagent or siRNA to Hes1 delivered by PLGA nanoparticles decreased Hes1 mRNA and up-regulated Atoh1 mRNA expression allowing supporting cells (SCs) to acquire a HC fate. Experiments using cochleae and maculae of p27kip1/-GFP transgenic mouse pups demonstrated that newly generated HCs trans-differentiated from SCs. Furthermore, PLGA nanoparticles are non-toxic to inner ear tissue, readily taken up by cells within the tissue of interest, and present a synthetic delivery system that is a safe alternative to viral vectors. These results indicate that when delivered using a suitable vehicle, Hes siRNAs are potential therapeutic molecules that may have the capacity to regenerate new HCs in the inner ear and possibly restore human hearing and balance function.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Hearing Research - Volume 304, October 2013, Pages 91-110
Journal: Hearing Research - Volume 304, October 2013, Pages 91-110
نویسندگان
Xiaoping Du, Wei Li, Xinsheng Gao, Matthew B. West, W. Mark Saltzman, Christopher J. Cheng, Charles Stewart, Jie Zheng, Weihua Cheng, Richard D. Kopke,