The cochlea is a highly complex organ consisting of several different types of cells that must coordinate their function for normal audition to occur. Typically, we assume that hearing loss is caused by the death or dysfunction of cochlear hair cells, which are the mechanosensory cells that transduce the mechanical energy from the traveling wave into neural impulses that the brain can interpret as sound. However, hearing loss can also be caused by the death or dysfunction of auditory neurons (auditory neuropathy), cochlear supporting cells (connexin 26 mutations), or the cells of the bony labyrinth that encase the organ (otosclerosis). Importantly, many common causes of hearing loss, such as noise-induced hearing loss, may be caused by the impairment of several different cell types.
Stem cell therapies, which aim to use immature stem cells to replace dead or damaged cochlear cells, are currently under investigation for the treatment of hearing loss. Cell-based therapies hold great promise as future therapies; however, there are significant technical hurdles that need to be addressed before they are ready for clinical use. The primary challenge is to ensure stem cell development into the anatomically appropriate cell type or types that are responsible for hearing loss.
Decellularized Ear Tissues as Scaffolds for Stem Cell Differentiation
Santi PA, Johnson SB J Assoc Res Otolaryngol 2013;14:3-15
One way of accomplishing this goal is to incubate the stem cells on a substrate that can then be used to replace the damaged parts of the cochlea, or even the cochlea in its entirety. Theoretically, if the substrate maintained a cochlear morphology, then local environmental cues would help to determine the appropriate cell fates of the stem cells. The recent study by Santi and Johnson at the University of Minnesota laid the foundation for this approach by developing a biological scaffolding that could be seeded with stem cells in future experiments. These investigators used different detergents to decellularize, or wash out, the native cells from human and mouse cochlea. The resulting tissue appeared to be a translucent weblike structure consisting of the extracellular matrix that remained from the initial tissue.
Under normal conditions, cells have no physical contact with each other. Rather, adjacent cells extend structural proteins from their cell surfaces that interact with similar proteins from neighboring cells to stabilize each other in space and provide internal signaling that may influence cellular development or function. The aggregate of these extracellular proteins is called the extracellular matrix.
Santi and Johnson have provided the first techniques for isolating the extracellular matrix of the cochlea. Their results varied depending upon the type of detergent used and the duration of exposure. A milder detergent left an extracellular matrix that had more accurate cochlear morphology but was accompanied by residual cellular debris. A more stringent detergent resulted in greater decellularization but a decrease in the morphology of the extracellular matrix. In both cases, treatment with the detergent did not allow for preservation of the fine detail of the organ of Corti or complete decellularization of the bony labyrinth.
While imperfect, these results are noteworthy because they represent the early stages of a potential treatment for hearing loss. The authors also describe this to be an encouraging preparation for the extracellular matrix of the spiral ganglion, where the neurons that innervate the hair cells reside.
Scientific progress rarely advances by leaps and bounds. More commonly, science advances incrementally. This paper is a solid example of this systematic process. Santi and Johnson present a preliminary step to create a biologically engineered cochlea that could someday be transplanted into deafened individuals. Much work is still needed in order to define the appropriate detergents and conditions that will yield a more complete extracellular matrix and to identity the components that comprise the resulting extracellular matrix.
Once these questions have been answered, the next step would be to seed this extracellular matrix with stem cells and differentiate them into appropriate cell types, which is no easy task. However, similar technology is currently being investigated in the heart, lung, trachea, and nervous system, with promising results. In this respect, researchers in the field of hearing loss are keeping pace with broader applications of stem cell therapies.