Stem cells as therapy for hearing loss

Department of Otolaryngology and Program in Neuroscience, Harvard Medical School and Eaton Peabody Laboratory, Massachusetts Eye and Ear Infirmary, Boston, MA 02114, USA.
Trends in Molecular Medicine (Impact Factor: 9.45). 08/2004; 10(7):309-15. DOI: 10.1016/j.molmed.2004.05.008
Source: PubMed


One of the greatest challenges in the treatment of inner-ear disorders is to find a cure for the hearing loss that is caused by the loss of cochlear hair cells or spiral ganglion neurons. The recent discovery of stem cells in the adult inner ear that are capable of differentiating into hair cells, as well as the finding that embryonic stem cells can be converted into hair cells, raise hope for the future development of stem-cell-based treatment regimens. Here, we propose different approaches for using stem cells to regenerate the damaged inner ear and we describe the potential obstacles that translational approaches must overcome for the development of stem-cell-based cell-replacement therapies for the damaged inner ear.

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Available from: Carleton Eduardo Corrales, Jul 29, 2014
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    • "other hearing disorders. Stem cells in the inner ear lack the capacity to differentiate and replace damaged hair cells (Li et al., 2004). Therefore, a cell source like hUCMSCs with the capacity to express Atoh1 may potentially be used in therapeutic applications. "
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    ABSTRACT: Abstract Hearing is one of our main sensory systems and having a hearing disorder can have a significant impact in an individual's quality of life. Sensory neural hearing loss (SNHL) is the most common form of hearing loss; it results from the degeneration of inner ear sensory hair cells and auditory neurons in the cochlea, cells that are terminally differentiated. Stem cell-and gene delivery-based strategies provide an opportunity for the replacement of these cells. In recent years, there has been an increasing interest in gene delivery to mesenchymal stem cells. In this study, we evaluated the potential of human umbilical cord mesenchymal stromal cells (hUCMSCs) as a possible source for regenerating inner ear hair cells. The expression of Atoh1 induced the differentiation of hUCMSCs into cells that resembled inner ear hair cells morphologically and immunocytochemically, evidenced by the expression of hair cell-specific markers. The results demonstrated for the first time that hUCMSCs can differentiate into hair cell-like cells, thus introducing a new potential tissue engineering and cell transplantation approach for the treatment of hearing loss.
    02/2013; 15(1):43-54. DOI:10.1089/cell.2011.0097
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    • "One end of hair cells interacts with physical inputs and transmits these signals to the neural circuits, linked to the opposite end of the cell by a synapsis[1]. Most types of congenital and acquired hearing loss arise from damage and irreversible loss of cochlear hair cells or their associated neurons[2]. "
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    ABSTRACT: Culturing otospheres from dissociated organ of Corti is an appropriate starting point aiming at the development of cell therapy for hair cell loss. Although guinea pigs have been widely used as an excellent experimental model for studying the biology of the inner ear, the mouse cochlea has been more suitable for yielding otospheres in vitro. The aim of this study was to compare conditions and outcomes of otosphere suspension cultures from dissociated organ of Corti of either mouse or guinea pig at postnatal day three (P3), and to evaluate the guinea pig as a potential cochlea donor for preclinical cell therapy. Organs of Corti were surgically isolated from P3 guinea pig or mouse cochlea, dissociated and cultivated under non-adherent conditions. Cultures were maintained in serum-free DMEM:F12 medium, supplemented with epidermal growth factor (EGF) plus either basic fibroblast growth factor (bFGF) or transforming growth factor alpha (TGFα). Immunofluorescence assays were conducted for phenotype characterization. The TGFα group presented a number of spheres significantly higher than the bFGF group. Although mouse cultures yielded more cells per sphere than guinea pig cultures, sox2 and nestin distributed similarly in otosphere cells from both organisms. We present evidence that otospheres retain properties of inner ear progenitor cells such as self-renewal, proliferation, and differentiation into hair cells or supporting cells. Dissociated guinea pig cochlea produced otospheres in vitro, expressing sox2 and nestin similarly to mouse otospheres. Our data is supporting evidence for the presence of inner ear progenitor cells in the postnatal guinea pig. However, there is limited viability for these cells in neonatal guinea pig cochlea when compared to the differentiation potential observed for the mouse organ of Corti at the same developmental stage.
    Journal of Translational Medicine 11/2010; 8(1):119. DOI:10.1186/1479-5876-8-119 · 3.93 Impact Factor
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    • "Various attempts have been made to transform, through stepwise changes of culture medium allowing exposure to various factors, the potential of stem cells derived from several different sources into hair-cell like cells showing specific hair cell markers (Jeon et al. 2007; Li et al. 2004; Senn and Heller 2008). Stem cells derived from several sources such as bone marrow (Jeon et al. 2007), various neural tissues (Tamura et al. 2004; Tateya et al. 2003), or neurosensory precursors (Hu et al. 2005) have been tested for their capacity to develop into hair-cell-like cells and to survive when injected into the ear, generating a substantial body of literature indicating how best to implant cells for neuronal (Corrales et al. 2006; Martinez-Monedero et al. 2006; Tamura et al. 2004; Tateya et al. 2003; Ulfendahl et al. 2007) or sensory (Iguchi et al. 2004; Li et al. 2004; Naito et al. 2004; Nakagawa and Ito 2005) replacement. Overall, the data are encouraging as they indicate that the technical problem of how to implant properly primed precursors into the cochlea or modiolus for hair cell and sensory neuron replacement is solvable. "
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    ABSTRACT: Many elderly people worldwide lose the neurosensory part of their ear and turn deaf. Cochlear implants to restore some hearing after neurosensory hearing loss are, at present, the only therapy for these people. In contrast to this therapy, replacement of hair cells via stem cell therapies holds the promise for a cure. We review here current insights into embryonic, adult, and inducible stem cells that might provide cells for seeding the cochlea with the hope of new hair cell formation. We propose a two-step approach using a first set of transcription factors to enhance the generation of inducible pluripotent stem (iPS) cells and a second set of factors to initiate the differentiation of hair cells. Recent evidence regarding ear development and stem cell research strongly suggest that microRNAs will be an important new regulatory factor in both iPS cell formation and differentiation to reprogram cells into hair cells. In addition, we highlight currently insurmountable obstacles to the successful transformation of stem cells into hair cell precursors and their injection into the cochlear canal to replace lost hair cells.
    Cell and Tissue Research 07/2008; 333(3):373-9. DOI:10.1007/s00441-008-0639-z · 3.57 Impact Factor
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