Stem+Cell+Therapy+for+the+Treatment+of+Hearing+Loss

=**Introduction **= toc

Sensorineural hearing loss is a form of deafness that is acquired in humans by a mixture of factors, such as: trauma, viruses, medications/ drugs and exposure to loud noises [1]. Hearing loss is one of the most common disabilities in the world, effecting roughly 5% of people [2], [23]. Sensorineural hearing loss is typically irreversible, because the body has no mechanism for repairing the inner ear. The field of regenerative medicine, or stem cell therapy, hopes to provide cures for “[diseases] which cannot be cured by conventional medicines” [6]. Interest in the use of stem cells to cure human deafness began in the 1980’s with a study on avian hearing loss. It has since become a heavily researched field. Since the original research was published, studies have tested the efficacy of treatments in both in-vitro and in-vivo environments with a multitude of different animals. The latest research has focused on controlling the actions of implanted cells, reducing cancer risk, and even includes a limited human trial.

=**Sensorineural Hearing Loss **=

Sensorineural hearing loss is typically caused by damage to the fragile components of the inner ear and cochlea. Within the human cochlea there are roughly 10,000 microscopic hairs, shown in Figure 1. These hairs move with the vibrations of sound waves, which is then detected by the spiral neurons of the inner ear. The nerve signals are then sent to the auditory nerve for interpretation by the brain. Certain medications and drugs, head trauma, viral infections, and exposure to loud noises can cause swelling, fatigue and even the destruction of the microscopic hairs. The destruction of the hairs and spiral neurons results in hearing loss. Hearing loss has varying severities, from losing the ability to detect certain pitches of sound to complete deafness. While many organs in the human body are capable of self-repair, the cochlea and the sensory hairs of the inner ear are not regenerative [7]. This means that hearing loss in humans is currently irreversible.

Hearing loss is a particularly debilitating condition because it affects communication, one of the most important traits of our species. However, the impacts of hearing loss go far beyond communication. Studies show “…that uncorrected hearing loss gives rise to poorer quality of life, related to isolation, reduced social activity, and a feeling of being excluded, leading to an increased prevalence of symptoms of depression.” It has also been found that hearing loss causes cognitive decline, such as long and short term memory loss [4].

=**Current Treatments **=

The most common current treatments for sensorineural hearing loss are hearing aids and cochlear implants. They are electronic prosthetic devices designed to assist the deaf with understanding conversation, but they are not designed to restore normal hearing to those who wear them [1]. This is especially important when considering cochlear implants, which are devices implanted inside the ear, attached directly to the auditory nerve. The National Institute on Deafness and Other Communication Disorders states that a cochlear implant is not designed to restore normal hearing, but rather give “…a deaf person a useful representation of sounds in the environment and help him or her to understand speech” [3]. A basic diagram of a cochlear implant is shown in Figure 2.

Hearing aids and cochlear implants are very helpful devices for those who use them, but they fall short of restoring normal hearing. Recent studies in the UK have shown that hearing aids also fall short of preventing the long and short term memory loss that is associated with hearing loss [5], [21]. The search for an alternative solution to hearing loss has looked towards stem cell research for many years [11].

=**Stem Cells **=

Stem cells are a type of cell that can be found in almost every plant and animal. They are cells whose purpose is to heal and regenerate tissues, bone and even neurons. They are purposefully variable and can ‘differentiate’ into many different cell types and then duplicate themselves. This trait makes them perfect candidates for regenerating damaged parts of the body [20]. There are two main sources for human stem cells: adult stem cells and embryonic stem cells. Embryonic stem cells have been surrounded by debate for several years over ethical concerns. Embryonic cells are the more variable of the two types of stem cells, which makes them extremely versatile. They are, however, in shorter supply because there are few sources of them [24]. One of the most important factors is that embryonic stem cells pose a higher risk of forming cancer [14]. Adult stem cells are less variable than embryonic cells are. This means that only certain types of adult cells can only differentiate into certain types [6]. This means that while adult stem cells require more manipulation to use, they have the lowest risk.

New research into adult stem cells and the biological factors that control them is showing that they could have higher differentiability than initially thought. Adult pluripotent stem cells are genetically modified adult cells that act as if they were embryonic cells. This means that one’s own skin cells could be used to cure their hearing loss. In 2016, Dr. Mahla of the Indian Institute of Science Education and Research, estimated that by the year 2020, we could expect to be able to produce a wide array of tissues and organs from adult stem cells [6]. Although the future cure for hearing loss may not be stem cell therapies, the current state of this research is promising [2], [12], [16].

**Early Research **
Interest in regenerative medicine as a treatment for hearing loss was first started after a 1988 study on avian hearing loss was published. The landmark study showed that the injection of stem cells into the ears of deaf chickens greatly improved their hearing. While this technique ultimately did not translate directly to mammals and humans, the study nonetheless showed that hearing loss was not necessarily irreversible [17].

The study on chickens spurred on several additional studies which looked to test the actions of stem cells in the cochlea of different types of mammals. These studies included deaf mice [8], [9], [19] and guinea pigs [10] as models of human hearing loss. These studies were specifically focused on the survival rate of grafted stem cells within the cochlea and how they differentiated. The focuses of the studies were not to determine whether or not hearing improved, rather they just focused on the transformations that the cells experienced within the cochlea. These studies found promising results, showing that not only did most of the grafted cells survive, many of them differentiated into hair cells.

A study completed in 2011 was one of the first to quantitatively test the improvements in hearing loss with human stem cells. This study was completed on immunosuppressed mice, who had been inbreed to induce hearing loss. It found that the hearing loss was substantially reversed within the mice after just 4 weeks post-surgery [18].

**State of the Art **
The current state of stem cell research for the treatment of hearing loss could be best described as ‘fine tuning.’ Over the last few years, a large volume of research has come out that investigates different techniques to control the actions of the cells. In-vitro studies have found that grafted stem cells can reliably differentiate into and then repair sensory hair cells and spiral neurons. However, in-vivo studies have found that the results are less reliable when working inside of living cochleas. These difficulties are what have prompted the focus on controlling the cells when they are grafted into the cochlea. Researchers have looked at solutions such as grafting different cell types, changing genes and biological processes, and even using electrical stimulation to promote certain types of growth.

Three major types of adult stem cells have been experimented with to determine the ideal candidate for grafting into the cochlea. In mice: neural, olfactory, and bone marrow stem cells have been experimented with. Neural stem cells were extracted from the brains of mice and guinea pigs, and were found to reliably differentiate into sensory hair and spiral neuron cell types when injected into the damaged cochlea [8] – [10]. Next, olfactory stem cells, extracted from a biopsy of the inner nose of mice found that the grafted stem cells differentiated properly into hair and neuron cells. Not only did they survive for the 4 weeks until testing, the hearing thresholds of the treated mice improved substantially [18], [22]. Lastly, the bone marrow of mice was tested as an implant of stem cells into the ears of hearing impaired mice. The study found that the hearing in the mice did not improve, and that very few of the cells expressed markers showing that they had differentiated into hair or neuron cells [11]. While neural and olfactory cells seem better poised to serve as sources of stem cells for hearing loss, more research is needed to disprove the potential usefulness of bone marrow stem cells. An additional factor being considered by researchers, is the relative ease and safety of extracting olfactory stem cells versus neural stem cells. Given ongoing research into adult pluripotent stem cells, skin cells could someday be a potential source for the stem cells being grafted into human cochlea [24].

Beyond types of cells, researchers have begun experimenting with changing genetic and biological factors to control differentiation of the stem cells. Rutgers University released a study in 2017 that focused on the effects of the “overexpression” of the gene NEUROG1. This gene controls the rate of multiplication of cells within the body, and could help force implanted stem cells to heal faster and more completely. The overexpression of the gene, however, could lead to an increased risk of cancer forming at the locations of the cell grafts [14]. A study by Hamadan University in Iran found that the “miR-183 cluster” of DNA was section of DNA that controlled differentiation of stem cells. It found that by manipulating that area of DNA in mice and zebrafish, they were able to increase the “neuroregenerative capacity” of the grafted cells for treating hearing loss [2]. Finally, researchers have focused on controlling the differentiation and excessive growth of stem cells by limiting cell to cell communication. This is referred to as “notch inhibition” and research has shown that this limiting factor can help induce regeneration of the cochlear hair cells [7]. Through future research, it may be found that one, several or none of these factors are the key to making stem cell therapies work effectively and safely in humans.

Another effort by researchers to fine tune and control the stem cells grafted into a cochlea is physical measures. A study in 2013 investigated a potential solution to the difficulties that the individual “microenvironments” of the inner ear poses to the control of stem cells. It has been found that the cochlea’s complex structure makes the differentiation of the stem cells difficult to control. The study proposed the potential use of electrical fields to encourage differentiation of the cells. Past research found that when stem cells are in the presence of small electrical fields, they differentiate into certain types of cells, depending on the intensity of the field. The proposal is that specific intensity of electrical fields could be used to force the cells to differentiate into neurons when inside of the cochlea [15]. Again, further research will be needed to determine the viability of electrical fields as a way to improve the use of stem cells to treat hearing loss.

For the first time in the US, a study involving humans to test stem cells as a treatment for hearing loss is underway. Although the results of the study have not yet been released it is a promising sign that it was initiated. While the study only involves 10 children [13], the outcomes could determine the future of stem cell research as a cure for hearing loss. See the hyperlinks below for the US government site where the results will eventually be published as well as the press release for the study, which gives a quick overview of what it means.

=**Conclusion **=

Despite the large volume of existing research into stem cells and their potential for reversing hearing loss, the verdict is still unknown as to whether or not they are the solution. Past and recent studies on multiple mammalian models of hearing loss have shown that stem cells have potential to reduce the intensity of hearing loss. However, the use of stem cells within the ears of humans is still being tested at the small scale because of the difficulties of controlling the actions of the cells. The microscopic environments of the inner cochlea are difficult to control and grafts of stem cells have the potential to grow incorrectly or to even become cancerous [14]. With further research and soon the results of the ongoing human trial at the Children’s Hospital of Florida, the future of hearing loss treatment will become clearer. Hearing loss could soon be treated with an adult’s own stem cells, signaling the end of deafness for humans.

=**Bibliography **=

[1] Hearing Loss Association of America. (Accessed June 13, 2018). Types, Causes and Treatment. Retrieved from https://www.hearingloss.org/hearing-help/hearing-loss-basics/types-causes-and-treatment

[2] Mahmoudian-Sani, M., Mehri-Ghahfarrokhi, A., Poorshahbazi, G., & Asadi-Samani, M. (2017). The application of mir-183 family and mesenchymal stem cells: A possibility for restoring hearing loss. Indian Journal of Otology, 23(4) doi:http://dx.doi.org.colorado.idm.oclc.org/10.4103/indianjotol.INDIANJOTOL_105_17

[3] National Institute on Deafness and Other Communication Disorders. “Cochlear Implants.” NIDCD, February 2016, https://www.nidcd.nih.gov/health/cochlear-implants

[4] Arlinger S. (2003) Negative consequences of uncorrected hearing loss – A review. International Journal of Audiology 42(2), 17 – 20.

[5] Rönnberg, J., Hygge, S., Keidser, G., Rudner, M. (2014). The effect of functional hearing loss and age on long- and short-term visuospatial memory: evidence from the UK biobank resource. Frontiers of Aging Neuroscience. doi: https://doi.org/10.3389/fnagi.2014.00326

[6] Mahla, R. S. (2016). Stem Cells Applications in Regenerative Medicine and Disease Therapeutics. International Journal of Cell Biology. doi: 6940283.

[7] Mizutari K., Fujioka M., Hosoya M., et al. (2013) Notch inhibition induces cochlear hair cell regeneration and recovery of hearing after acoustic trauma. Neuron. 77(1), 58–69.

[8] Ito, J., Kojima, K., & Kawaguchi, S. (2001) Survival of neural stem cells in the cochlea. Acta Oto-Laryngologica. 121(2), 140-142.

[9] Tateya, I., Nakagawa, T., Iguchi, F. et al. (2003) Fate of neural stem cells grafted into injured inner ears of mice. Neuroreport, vol. 14, no. 13, 1677–1681.

[10] Parker, M. A., Corliss, D. A., Gray, B. et al. (2007) Neural stem cells injected into the sound-damaged cochlea migrate throughout the cochlea and express markers of hair cells, supporting cells, and spiral ganglion cells. Hearing Research, vol. 232, no. 1-2, 29–43.

[11] Ajalloueyan, M., et al. (2013) Stem Cell Transplantation in Noise Induced Hearing Loss. International Journal of Pediatric Otorhinolaryngology 77(4), 469 – 472.

[12] Parker, M., Cotanche D. (2004) The potential use of stem cells for cochlear repair. Trends in Molecular Medicine 10(7) pp 72 – 80.

[13] Cord Blood Registry. “FDA-Regulated Study of Cord Blood Stem Cells to Treat Acquired Hearing Loss Launches.” CordBlood.com, 2018, https://www.cordblood.com/press-release/hearing-loss.

[14] Rutgers University. “Inner Ear Stem Cells May Someday Restore Hearing.” ScienceDaily, 7 Nov. 2017, www.sciencedaily.com/releases/2017/11/171107092626.htm.

[15] Tang, M., Yan, X., Tang, Q., Guo, R., Da, P. & Li, D. (2018) Potential Application of Electrical Stimulation in Stem Cell-Based Treatment against Hearing Loss. Neural Plasticity, 1 – 6.

[16] Li, H., Corrales, C., Edge, A. & Heller, S. (2004). Stem cells as therapy for hearing loss. Trends in Molecular Medicine, 10(7), 309 – 315. doi: https://doi-org.colorado.idm.oclc.org/10.1016/j.molmed.2004.05.008

[17] Corwin J. T., Cotanche D. A. (1988) Regeneration of sensory hair cells after acoustic trauma. Science. 240, 1772 – 1774.

[18] Pandit, S. R., Sullivan, J. M., Egger, V., Borecki, A. A. and Oleskevich, S. (2011), Functional Effects of Adult Human Olfactory Stem Cells on Early‐Onset Sensorineural Hearing Loss. STEM CELLS, 29, 670-677. doi:10.1002/stem.609

[19] Sullivan, J., et al. (2011). Effect of epithelial stem cell transplantation on noise induced hearing loss in adult mice. Neurobiology of Disease, 41(2), 552 – 559. doi: https://doi.org/10.1016/j.nbd.2010.11.001

[20] Harvard Stem Cell Institute. “Hearing Loss.” HSC, 2018, https://hsci.harvard.edu/hearing-loss-0

[21] Dawes, P., et al. (2015). Hearing Loss and Cognition: The Role of Hearing Aids, Social Isolation and Depression. Public Library of Science. doi: https://doi.org/10.1371/journal.pone.0119616

[22] Xu, Y., et al. (2016). Olfactory epithelium neural stem cell implantation restores noise-induced hearing loss in rats. Neuroscience Letters, 616, 19-25. doi: https://doi-org.colorado.idm.oclc.org/10.1016/j.neulet.2016.01.016

[23] Niskar, AS, et al. Prevalence of hearing loss among children 6 to 19 years of age: the Third National Health and Nutrition Examination Survey. JAMA.1998; 279:1071-1075.

[24] The Mayo Clinic. (2013, March 23). Stem cells: What they are and what they do. Retrieved from https://www.mayoclinic.org/tests-procedures/bone-marrow-transplant/in-depth/stem-cells/art-20048117

Links: [|Living with deafness in a hearing world] [|Ongoing clinical trial for pediatric hearing loss] [|Press release for the ongoing human trial] [|Sensorineural Hearing loss resources] [|Ted Talk discussing the potentials of stem cell research] ** Stem Cell Therapy for the Treatment of Hearing Loss Sensorineural hearing loss is a form of deafness that is acquired in humans by a mixture of factors, such as: trauma, viruses, medications/ drugs and exposure to loud noises [1]. Hearing loss is one of the most common disabilities in the world, effecting roughly 5% of people [2] [23]. Sensorineural hearing loss is typically irreversible, because the body has no mechanism for repairing the inner ear. The field of regenerative medicine, or stem cell therapy, hopes to provide cures for “[diseases] which cannot be cured by conventional medicines” [6]. Interest in the use of stem cells to cure human deafness began in the 1980’s with a study on avian hearing loss. It has since become a heavily researched field. Since the original research was published, studies have tested the efficacy of treatments in both in-vitro and in-vivo environments with a multitude of different animals. The latest research has focused on controlling the actions of implanted cells, reducing cancer risk, and even includes a limited [|human trial]. Sensorineural Hearing Loss Sensorineural hearing loss is typically caused by damage to the fragile components of the inner ear and cochlea. Within the human cochlea there are roughly 10,000 microscopic hairs, shown in Figure 1. These hairs move with the vibrations of sound waves, which is then detected by the spiral neurons of the inner ear. The nerve signals are then sent to the auditory nerve for interpretation by the brain. Certain medications and drugs, head trauma, viral infections, and exposure to loud noises can cause swelling, fatigue and even the destruction of the microscopic hairs. The destruction of the hairs and spiral neurons results in hearing loss. Hearing loss has varying severities, from losing the ability to detect certain pitches of sound to complete deafness. While many organs in the human body are capable of self-repair, the cochlea and the sensory hairs of the inner ear are not regenerative [7]. This means that hearing loss in humans is currently irreversible. Hearing loss is a particularly debilitating condition because it affects communication, one of the most important traits of our species. However, the impacts of hearing loss go far beyond communication. Studies show “… that uncorrected hearing loss gives rise to poorer quality of life, related to isolation, reduced social activity, and a feeling of being excluded, leading to an increased prevalence of symptoms of depression.” It has also been found that hearing loss causes cognitive decline, such as long and short term memory loss [4]. Current Treatments The most common current treatments for sensorineural hearing loss are hearing aids and cochlear implants. They are electronic prosthetic devices designed to assist the deaf with understanding conversation, but they are not designed to restore normal hearing to those who wear them [1]. This is especially important when considering cochlear implants, which are devices implanted inside the ear, attached directly to the auditory nerve. The National Institute on Deafness and Other Communication Disorders states that a cochlear implant is not designed to restore normal hearing, but rather give “… a deaf person a useful representation of sounds in the environment and help him or her to understand speech ” [3]. A basic diagram of a cochlear implant is shown in Figure 2. Hearing aids and cochlear implants are very helpful devices for those who use them, but they fall short of restoring normal hearing. Recent studies in the UK have shown that hearing aids also fall short of preventing the long and short term memory loss that is associated with hearing loss [5] [21]. The search for an alternative solution to hearing loss has looked towards stem cell research for many years [11]. Stem Cells Stem cells are a type of cell that can be found in almost every plant and animal. They are cells whose purpose is to heal and regenerate tissues, bone and even neurons. They are purposefully variable and can ‘differentiate’ into many different cell types and then duplicate themselves. This trait makes them perfect candidates for regenerating damaged parts of the body [20]. There are two main sources for human stem cells: those are adult stem cells and embryonic stem cells. Embryonic stem cells have been surrounded by debate for several years over ethical concerns. Embryonic cells are the more variable of the two types of stem cells, which makes them extremely versatile. They are, however, in shorter supply because of the ethical debate that surrounds them [24]. One of the most important factors is that embryonic stem cells pose a higher risk of forming cancer [14]. Adult stem cells are less variable than embryonic cells are. This means that only certain types of adult cells can only differentiate into certain types [6]. This means that while adult stem cells require more manipulation to use, they have the lowest risk. New research into adult stem cells and the biological factors that control them is showing that they could have higher differentiability than initially thought. Adult pluripotent stem cells are genetically modified adult cells that act as if they were embryonic cells. This means that one’s own skin cells could be used to cure their hearing loss. In 2016, Dr. Mahla of the Indian Institute of Science Education and Research, estimated that by the year 2020, we could expect to be able to produce a wide array of tissues and organs from adult stem cells [6]. Although the future cure for hearing loss may not be stem cell therapies, the current state of this research is promising [2], [12], [16]. Early Research Interest in regenerative medicine as a treatment for hearing loss was first started after a 1988 study on avian hearing loss was published. The landmark study showed that the injection of stem cells into the ears of deaf chickens greatly improved their hearing. While this technique ultimately did not translate directly to mammals and humans, the study nonetheless showed that hearing loss was not necessarily irreversible [17]. The study on chickens spurred on several additional studies which looked to test the actions of stem cells in the cochlea of different types of mammals. These studies included deaf mice [8], [9], [19] and guinea pigs [10] as models of human hearing loss. These studies were specifically focused on the survival rate of grafted stem cells within the cochlea and how they differentiated. The focuses of the studies were not to determine whether or not hearing improved, rather they just focused on the transformations that the cells experienced within the cochlea. These studies found promising results, showing that not only did most of the grafted cells survive, many of them differentiated into hair cells. A study completed in 2011 was one of the first to quantitatively test the improvements in hearing loss with human stem cells. This study was completed on immunosuppressed mice, who had been inbreed to induce hearing loss. It found that the hearing loss was substantially reversed within the mice after just 4 weeks post-surgery [18]. State of the Art The current state of stem cell research for the treatment of hearing loss could be best described as ‘fine tuning.’ Over the last few years, a large volume of research has come out that investigates different techniques to control the actions of the cells. In-vitro studies have found that grafted stem cells can reliably differentiate into and then repair sensory hair cells and spiral neurons. However, in-vivo studies have found that the results are less reliable when working inside of living cochleas. These difficulties are what have prompted the focus on controlling the cells when they are grafted into the cochlea. Researchers have looked at solutions such as grafting different cell types, changing genes and biological processes, and even using electrical stimulation to promote certain types of growth. Three major types of adult stem cells have been experimented with to determine the ideal candidate for grafting into the cochlea. In mice: neural, olfactory, and bone marrow stem cells have been experimented with. Neural stem cells were extracted from the brains of mice and guinea pigs, and were found to reliably differentiate into sensory hair and spiral neuron cell types when injected into the damaged cochlea [8] – [10]. Next, olfactory stem cells, extracted from a biopsy of the inner nose of mice found that the grafted stem cells differentiated properly into hair and neuron cells. Not only did they survive for the 4 weeks until testing, the hearing thresholds of the treated mice improved substantially [18], [22]. Lastly, the bone marrow of mice was tested as an implant of stem cells into the ears of hearing impaired mice. The study found that the hearing in the mice did not improve, and that very few of the cells expressed markers showing that they had differentiated into hair or neuron cells [11]. While neural and olfactory cells seem better poised to serve as sources of stem cells for hearing loss, more research is needed to disprove the potential usefulness of bone marrow stem cells. An additional factor being considered by researchers, is the relative ease and safety of extracting olfactory stem cells versus neural stem cells. Given ongoing research into adult pluripotent stem cells, skin cells could someday be a potential source for the stem cells being grafted into human cochlea [24]. Beyond types of cells, researchers have begun experimenting with changing genetic and biological factors to control differentiation of the stem cells. Rutgers University released a study in 2017 that focused on the effects of the “overexpression” of the gene NEUROG1. This gene controls the rate of multiplication of cells within the body, and could help force implanted stem cells to heal faster and more completely. The overexpression of the gene, however, could lead to an increased risk of cancer forming at the locations of the cell grafts [14]. A study by Hamadan University in Iran found that the “ miR-183 cluster” of DNA was section of DNA that controlled differentiation of stem cells. It found that by manipulating that area of DNA in mice and zebrafish, they were able to increase the “neuroregenerative capacity” of the grafted cells for treating hearing loss [2]. Finally, researchers have focused on controlling the differentiation and excessive growth of stem cells by limiting cell to cell communication. This is referred to as “notch inhibition” and research has shown that this limiting factor can help induce regeneration of the cochlear hair cells [7]. Through future research, it may be found that one, several or none of these factors are the key to making stem cell therapies work effectively and safely in humans. Another effort by researchers to fine tune and control the stem cells grafted into a cochlea is physical measures. A study in 2013 investigated a potential solution to the difficulties that the individual “microenvironments” of the inner ear poses to the control of stem cells. It has been found that the cochlea’s complex structure makes the differentiation of the stem cells difficult to control. The study proposed the potential use of electrical fields to encourage differentiation of the cells. Past research found that when stem cells are in the presence of small electrical fields, they differentiate into different types of cells, depending on the intensity of the field. The proposal is that specific intensity of electrical fields could be used to force the cells to differentiate into neurons [15]. Again, further research will be needed to determine the viability of electrical fields as a way to improve the use of stem cells to treat hearing loss. For the first time in the US, a study involving humans to test stem cells as a treatment for hearing loss is underway. Although the results of the study have not yet been released it is a promising sign that it was initiated. While the study only involves 10 children [13], the outcomes could determine the future of stem cell research as a cure for hearing loss. See the hyperlink below for the US government site where the results will eventually be published. Conclusion Despite the large volume of existing research into stem cells and their potential for reversing hearing loss, the verdict is still unknown as to whether or not they are the solution. Past and recent studies on multiple mammalian models of hearing loss have shown that stem cells have potential to reduce the intensity of hearing loss. However, the use of stem cells within the ears of humans is still being tested at the small scale because of the difficulties of controlling the actions of the cells. The microscopic environments of the inner cochlea are difficult to control and grafts of stem cells have the potential to grow incorrectly or to even become cancerous [14]. With further research and soon the results of the ongoing human trial at the Children’s Hospital of Florida, the future of hearing loss treatment will become clearer. One day, hearing loss could be treated with an adult’s own stem cells. Bibliography [1] Hearing Loss Association of America. (Accessed June 13, 2018). Types, Causes and Treatment. Retrieved from https://www.hearingloss.org/hearing-help/hearing-loss-basics/types-causes-and-treatment [2] Mahmoudian-Sani, M., Mehri-Ghahfarrokhi, A., Poorshahbazi, G., & Asadi-Samani, M. (2017). The application of mir-183 family and mesenchymal stem cells: A possibility for restoring hearing loss. Indian Journal of Otology, 23(4) doi:http://dx.doi.org.colorado.idm.oclc.org/10.4103/indianjotol.INDIANJOTOL_105_17 [3] National Institute on Deafness and Other Communication Disorders. “Cochlear Implants.” NIDCD, February 2016, https://www.nidcd.nih.gov/health/cochlear-implants [4] Arlinger S. (2003) Negative consequences of uncorrected hearing loss – A review. International Journal of Audiology 42(2), 17 – 20. [5] Rönnberg, J., Hygge, S., Keidser, G., Rudner, M. (2014). The effect of functional hearing loss and age on long- and short-term visuospatial memory: evidence from the UK biobank resource. Frontiers of Aging Neuroscience. doi: https://doi.org/10.3389/fnagi.2014.00326 [6] Mahla, R. S. (2016). Stem Cells Applications in Regenerative Medicine and Disease Therapeutics. International Journal of Cell Biology. doi: 6940283. [7] Mizutari K., Fujioka M., Hosoya M., et al. (2013) Notch inhibition induces cochlear hair cell regeneration and recovery of hearing after acoustic trauma. Neuron. 77(1), 58–69. [8] Ito, J., Kojima, K., & Kawaguchi, S. (2001) Survival of neural stem cells in the cochlea. Acta Oto-Laryngologica. 121(2), 140-142. [9] Tateya, I., Nakagawa, T., Iguchi, F. et al. (2003) Fate of neural stem cells grafted into injured inner ears of mice. Neuroreport, vol. 14, no. 13, 1677–1681. [10] Parker, M. A., Corliss, D. A., Gray, B. et al. (2007) Neural stem cells injected into the sound-damaged cochlea migrate throughout the cochlea and express markers of hair cells, supporting cells, and spiral ganglion cells. Hearing Research, vol. 232, no. 1-2, 29–43. [11] Ajalloueyan, M., et al. (2013) Stem Cell Transplantation in Noise Induced Hearing Loss. International Journal of Pediatric Otorhinolaryngology 77(4), 469 – 472. [12] Parker, M., Cotanche D. (2004) The potential use of stem cells for cochlear repair. Trends in Molecular Medicine 10(7) pp 72 – 80. [13] Cord Blood Registry. “FDA-Regulated Study of Cord Blood Stem Cells to Treat Acquired Hearing Loss Launches.” CordBlood.com, 2018, https://www.cordblood.com/press-release/hearing-loss. [14] Rutgers University. “Inner Ear Stem Cells May Someday Restore Hearing.” ScienceDaily, 7 Nov. 2017, www.sciencedaily.com/releases/2017/11/171107092626.htm. [15] Tang, M., Yan, X., Tang, Q., Guo, R., Da, P. & Li, D. (2018) Potential Application of Electrical Stimulation in Stem Cell-Based Treatment against Hearing Loss. Neural Plasticity, 1 – 6. [16] Li, H., Corrales, C., Edge, A. & Heller, S. (2004). Stem cells as therapy for hearing loss. Trends in Molecular Medicine, 10(7), 309 – 315. doi: https://doi-org.colorado.idm.oclc.org/10.1016/j.molmed.2004.05.008 [17] Corwin J. T., Cotanche D. A. (1988) Regeneration of sensory hair cells after acoustic trauma. Science. 240, 1772 – 1774. [18] Pandit, S. R., Sullivan, J. M., Egger, V., Borecki, A. A. and Oleskevich, S. (2011), Functional Effects of Adult Human Olfactory Stem Cells on Early‐Onset Sensorineural Hearing Loss. STEM CELLS, 29, 670-677. doi:10.1002/stem.609 [19] Sullivan, J., et al. (2011). Effect of epithelial stem cell transplantation on noise induced hearing loss in adult mice. Neurobiology of Disease, 41(2), 552 – 559. doi: https://doi.org/10.1016/j.nbd.2010.11.001 [20] Harvard Stem Cell Institute. “Hearing Loss.” HSC, 2018, https://hsci.harvard.edu/hearing-loss-0 [21] Dawes, P., et al. (2015). Hearing Loss and Cognition: The Role of Hearing Aids, Social Isolation and Depression. Public Library of Science. doi: https://doi.org/10.1371/journal.pone.0119616 [22] Xu, Y., et al. (2016). Olfactory epithelium neural stem cell implantation restores noise-induced hearing loss in rats. Neuroscience Letters, 616, 19-25. doi: https://doi-org.colorado.idm.oclc.org/10.1016/j.neulet.2016.01.016 [23] Niskar, AS, et al. Prevalence of hearing loss among children 6 to 19 years of age: the Third National Health and Nutrition Examination Survey. JAMA.1998; 279:1071-1075. [24] The Mayo Clinic. (2013, March 23). Stem cells: What they are and what they do. Retrieved from https://www.mayoclinic.org/tests-procedures/bone-marrow-transplant/in-depth/stem-cells/art-20048117 Links: ([]) Ongoing clinical trial ([]) Press release for the ongoing human trial ([]) Sensorineural Hearing loss resources ([|https://www.ted.com/talks/susan_solomon_the_promise_of_research_with_stem_cells#t-50812]) Ted Talk discussing the potentials of stem cell research **