![]() In addition, the detailed pattern of lymphatic flow in the cochlea is still unknown. It is also doubtful whether the auditory HCs that were transplanted into the scala tympani will migrate into the scala media and other target areas such as the auditory epithelium through the basilar membrane or helicotrema. ![]() The surgical techniques mentioned above are also limited to accessing just the scala tympani in the basal turn of the cochlea. Even though surgically accessing the cochlea through the cochleostomy or round window approaches have been widely used for cochlear implantation surgery, the surgical process can still cause disturbance or disruption of cochlear homeostasis that can result in residual hearing loss and vertigo. The cochlea is further partitioned into the scala tympani, media and vestibule. Transplantation of cells into the cochlea is challenging because the cochlea is positioned deep inside of the skull and surrounded by hard bony structures. ![]() The above technique may not be applicable for the other possible target areas of the cochlea. So far, induced differentiation has only been towards HC-like cells. Using these signals should be considered in the directed differentiation of transplanted cells. Inducing cell differentiation may be possible since delta-notch, wnt, and lateral inhibitions between HCs and supporting cells are well known signals in cochlear and HC development. Transplantation of undifferentiated or partly differentiated cells and then inducing them to differentiate into the desired cells in the appropriate target area surrounded by supporting cells seem to be more feasible. It may be safe to assume that two cells are not alike in the auditory epithelium or in the cochlea as a whole. It seems that these differences are not limited to the HCs only. Moreover, these cells are quite different from the apex to the base and also show differences from the first to the third low ( Fig. One should remind that the HCs in the auditory epithelium are divided into the inner HCs and outer HCs which perform different functions. In other words, whether to transplant already well differentiated targeted cells or partly or undifferentiated cells that will, hopefully, differentiate into the desired cells in the target area. For example, a decision should be made whether to transplant totipotent cells to nullpotent cells. ![]() Second, the developmental stages (differentiated or undifferentiated) of SCs should be considered. Transplantation of human ESCs derived otic progenitors into the spiral ganglion (SG) resulted in these cells surviving with functional recovery in animal affected by auditory neuropathy. More recently, generation of functioning inner ear sensory epithelia from pluripotent SCs was reported. HC-like cells with mechano-sensitive functioning cilia can be generated from embryonal SCs (ESCs) and inducible pluripotent SCs. Auditory hair cells (HCs) can be replaced and hearing improved by Atoh1 gene therapy in deaf mammals. The creation of inner ear progenitor cells from murine embryonic SCs in vitro and integrating these progenitor cells into the developing inner ear at sites of epithelial injury expressing the HC markers has been reported. There have been outstanding progresses in these areas of research. If there are no cells capable of differentiation in the cochlea, then SCs would be feasible for treatment. If there are cells in the cochlea which have a potential to differentiate, their trans-differentiation would be more suitable for managing sensorineural hearing loss. This review discusses the recent advances in SC research in sensorineural hearing loss with the subsequent sections discussing the possible hurdles and limitations that currently preclude their clinical application. Recently, there have been tremendous developments from stem cells (SCs) research involving sensorineural hearing loss, but several limitations and obstacles persist in allowing these developments from continuing onto clinical applications. HCs damages typically occur in the early stage of injury and can result a permanent hearing loss. The auditory HCs are easily damaged by aging as well as during episodes of ototoxicity and acoustic trauma. Among these cells are the auditory hair cells (HCs), which are terminally and well differentiated unique cells which have lost their regenerative potential after development. ![]() In mammals, the auditory system, which includes the cochlea, has a very complex structure harboring many types of cells performing different functions. ![]()
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