Growth Factors as Potential Drugs for the Sensory Epithelia of the Ear

Corwin, JT; Warchol, ME; Ld, Saffer; Je, Finley; Gu, Rong; Pr, Lamber

doi:10.1002/9780470514863.ch12

Cited by 9 publications

(2 citation statements)

References 56 publications

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“…Several members of the FGF family and their corresponding FGF receptors are involved in the development and regeneration of hair cells. FGF‐2 is one of the most well known mitogenic and protective substances working in the inner ear, which has been proposed to fulfill a variety of functions during vertebrate inner ear development and within the mature sensory organ (Corwin et al, ). FGF‐2 protected cochlear hair cells in organotypic cultures from ototoxic damage in vitro in rats, possibly acting on FGF receptor 3 which is expressed in hair cells (Low et al, ), and FGF‐2 protects auditory hair cells from noise damage in guinea pigs in vivo (Zhai et al, ; Carnicero et al, ).…”

Section: Discussionmentioning

confidence: 99%

Growth factors have a protective effect on neomycin‐induced hair cell loss

Lou

Yuan

Xie

et al. 2014

Cell Biology International

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We have demonstrated that selected growth factors are involved in regulating survival and proliferation of progenitor cells derived from the neonatal rat organ of Corti (OC). The protective and regenerative effects of these defined growth factors on the injured organ of Corti were therefore investigated. The organ of Corti dissected from the Wistar rat pups (P3-P5) was split into apical, middle, and basal parts, explanted and cultured with or without neomycin and growth factors. Insulin-like growth factor-1 (IGF-1), fibroblast growth factor-2 (FGF-2), and epidermal growth factor (EGF) protected the inner hair cells (IHCs) and outer hair cells (OHCs) from neomycin ototoxicity. Using EGF, IGF-1, and FGF-2 alone induced no protective effect on the survival of auditory hair cells. Combining 2 growth factors (EGF + IGF-1, EGF + FGF-2, or IGF-1 + FGF-2) gave statistically protective effects. Similarly, combining all three growth factors effectively protected auditory hair cells from the ototoxic insult. None of the growth factors induced regeneration of hair cells in the explants injured with neomycin. Thus various combinations of the three defined factors (IGF-1, FGF-2, and EGF) can protect the auditory hair cells from the neomycin-induced ototoxic damage, but no regeneration was seen. This offers a possible novel approach to the treatment of hearing loss.

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Section: Discussionmentioning

confidence: 99%

Growth factors have a protective effect on neomycin‐induced hair cell loss

Lou

Yuan

Xie

et al. 2014

Cell Biology International

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“…In mammals, the OC loses its ability to create new hair cells in utero (Chen and Segil, 1999) and the vestibular epithelia (saccule and utricle) cease hair cell production shortly after birth (Ruben, 1967). However, despite apparent quiescence, adult mammalian vestibular tissues maintain limited regenerative capabilities (Warchol et al, 1993; Lambert, 1994; Rubel et al, 1995; Li and Forge, 1997; Zheng and Gao, 1997; Zheng et al, 1997; Kuntz and Oesterle, 1998; Ogata et al, 1999; Li et al, 2003; Oesterle et al, 2003; Martinez-Monedero et al, 2007; Oshima et al, 2007) that can be stimulated by treatment with growth factors (Lambert, 1994; Yamashita and Oesterle, 1995; Corwin et al, 1996; Zheng et al, 1997; Kuntz and Oesterle, 1998; Oesterle et al, 2003). In contrast, agents to stimulate proliferation in the completely quiescent mature OC remain elusive (Sobkowicz et al, 1992; Roberson and Rubel, 1994; Chardin and Romand, 1995; Sobkowicz et al, 1996; Sobkowicz et al, 1997; Zine and de Ribaupierre, 1998).…”

Section: Implications For Auditory Physiologymentioning

confidence: 99%

Cellular targets of estrogen signaling in regeneration of inner ear sensory epithelia

McCullar

Oesterle

2009

Hearing Research

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Estrogen signaling in auditory and vestibular sensory epithelia is a newly emerging focus propelled by the role of estrogen signaling in many other proliferative systems. Understanding the pathways with which estrogen interacts can provide a means to identify how estrogen may modulate proliferative signaling in inner ear sensory epithelia. Reviewed herein are two signaling families, EGF and TGFβ. Both pathways are involved in regulating proliferation of supporting cells in mature vestibular sensory epithelia and have well characterized interactions with estrogen signaling in other systems. It is becoming increasingly clear that elucidating the complexity of signaling in regeneration will be necessary for development of therapeutics that can initiate regeneration and prevent progression to a pathogenic state.

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Survival of bundleless hair cells and subsequent bundle replacement in the bullfrog's saccule

et al. 2002

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Our senses of hearing and balance depend upon hair cells, the sensory receptors of the inner ear. Millions of people suffer from hearing and balance deficits caused by damage to hair cells as a result of exposure to noise, aminoglycoside antibiotics, and antitumor drugs. In some species such damage can be reversed through the production of new cells. This proliferative response is limited in mammals but it has been hypothesized that damaged hair cells might survive and undergo intracellular repair. We examined the fate of bullfrog saccular hair cells after exposure to a low dose of the aminoglycoside antibiotic gentamicin to determine whether hair cells could survive such treatment and subsequently be repaired. In organ cultures of the bullfrog saccule a combination of time-lapse video microscopy, two-photon microscopy, electron microscopy, and immunocytochemistry showed that hair cells can lose their hair bundle and survive as bundleless cells for at least 1 week. Time-lapse and electron microscopy revealed stages in the separation of the bundle from the cell body. Scanning electron microscopy (SEM) of cultures fixed 2, 4, and 7 days after antibiotic treatment showed that numerous new hair bundles were produced between 4 and 7 days of culture. Further examination revealed hair cells with small repaired hair bundles alongside damaged remnants of larger surviving bundles. The results indicate that sensory hair cells can undergo intracellular self-repair in the absence of mitosis, offering new possibilities for functional hair cell recovery and an explanation for non-proliferative recovery.

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Growth Factors as Potential Drugs for the Sensory Epithelia of the Ear

Cited by 9 publications

References 56 publications

Growth factors have a protective effect on neomycin‐induced hair cell loss

Growth factors have a protective effect on neomycin‐induced hair cell loss

Cellular targets of estrogen signaling in regeneration of inner ear sensory epithelia

Survival of bundleless hair cells and subsequent bundle replacement in the bullfrog's saccule

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