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: 10.11). 08/2004; 10(7):309-15. DOI: 10.1016/j.molmed.2004.05.008
Source: PubMed

ABSTRACT 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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    • "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 · 3.33 Impact Factor
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    • "Angiogenesis and vasculogenesis are the two major processes contributing to neovascularization in organs and tissues (Losordo and Dimmeler 2004). Neovascularization is an important event during tissue repair and regeneration after injury. "
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    ABSTRACT: Application of ouabain to the round window membrane of the gerbil selectively induces the death of most spiral ganglion neurons and thus provides an excellent model for investigating the survival and differentiation of embryonic stem cells (ESCs) introduced into the inner ear. In this study, mouse ESCs were pretreated with a neural-induction protocol and transplanted into Rosenthal's canal (RC), perilymph, or endolymph of Mongolian gerbils either 1-3 days (early post-injury transplant group) or 7 days or longer (late post-injury transplant group) after ouabain injury. Overall, ESC survival in RC and perilymphatic spaces was significantly greater in the early post-injury microenvironment as compared to the later post-injury condition. Viable clusters of ESCs within RC and perilymphatic spaces appeared to be associated with neovascularization in the early post-injury group. A small number of ESCs transplanted within RC stained for mature neuronal or glial cell markers. ESCs introduced into perilymph survived in several locations, but most differentiated into glia-like cells. ESCs transplanted into endolymph survived poorly if at all. These experiments demonstrate that there is an optimal time window for engraftment and survival of ESCs that occurs in the early post-injury period.
    Journal of the Association for Research in Otolaryngology 07/2008; 9(2):225-40. DOI:10.1007/s10162-008-0119-x · 2.55 Impact Factor
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