On Stem Cell Therapy for Sensorineural Hearing Loss

For patients and families experiencing hearing limitations and concerned about daily conversations and environmental sounds, sensorineural hearing loss presents a significant barrier. This condition occurs when the hair cells in the inner ear, responsible for converting sound vibrations into electrical signals or auditory nerve impulses that transmit sound information to the brain, are damaged.

Once hair cells and auditory nerves are damaged, current medical science is unable to naturally regenerate them. Consequently, complete hearing recovery through conventional treatment methods is exceedingly difficult, and palliative therapy, primarily involving hearing aids or cochlear implants, becomes the central focus of treatment.

However, hearing aids are solely sound amplification devices; they do not restore the function of damaged cells. Cochlear implants also convert sound into electrical signals for transmission, but they present limitations regarding the fidelity of the original sound and the ability for auditory discrimination.

Amidst this situation, and with advancements in regenerative medicine, novel approaches to repairing damaged inner ear cells are garnering attention. Specifically, treatments employing stem cells represent an endeavor to regenerate inner ear hair cells and auditory nerves, with research actively progressing worldwide.

Why Is Sensorineural Hearing Loss Considered "Incurable"?

Hair cells, once damaged, do not regenerate.

Sound reaches the ear as air vibrations and is transmitted from the tympanic membrane to the inner ear (cochlea), located deeper within. There, a crucial role is played by specialized sensory cells known as 'hair cells'.

These hair cells function to convert sound vibrations into electrical signals and transmit them to the brain via the auditory nerve. In essence, they serve as a transducer, transforming incoming sound into signals comprehensible to the brain.

To illustrate this function analogously, the hair cell is a "precision microphone within the ear."

However, human hair cells possess the characteristic that once damaged, they do not naturally regenerate. When damaged by factors such as aging, loud noises, or medications such as anticancer agents, the damage is irreversible, leading to progressive hearing loss.

Hearing aids and cochlear implants cannot 'restore original sound.'

In contemporary medicine, sensorineural hearing loss is primarily managed with devices such as hearing aids and cochlear implants.

Hearing aids are devices that amplify ambient sounds and transmit them to the ear. However, even if the sound is amplified, if the hair cells are damaged, the sound cannot be accurately transduced. This is analogous to placing a loudspeaker in front of a damaged microphone — the recording quality will not improve.

A cochlear implant is a medical device that places electrodes in the inner ear and delivers sound signals directly to the auditory nerve as electrical stimulation. While effective for severe hearing loss, there are limitations in distinguishing subtle sound differences and comprehending speech in noisy environments.

Furthermore, surgery is required, which entails considerations of cost and physical burden. Given these circumstances, traditional medicine is widely considered ineffective in restoring lost hearing.

The concept of repairing the cells themselves

In this context, emphasis is placed on efforts to regenerate inner ear cells through regenerative medicine.

Research is particularly advancing in a technique known as stem cell therapy. Stem cells are cells with the capacity to differentiate into various cell types within the body and serve as "seeds of regeneration" that repair damaged tissue.

For sensorineural hearing loss, the objective is to deliver stem cells to the inner ear to stimulate the regeneration of damaged hair cells and auditory nerves.

The notion of regenerative medicine was once confined to the realm of speculation, but contemporary research is progressively transforming these possibilities into tangible realities. For individuals who find traditional medical approaches restrictive, Stem Cell Therapy presents itself as a promising alternative, opening up new avenues of potential.

Stem Cells for Sensorineural Hearing Loss and Treatment Options

The type of stem cell used

The cornerstone of regenerative medicine for sensorineural hearing loss is mesenchymal stem cells (MSCs). MSCs are derived from bone marrow, adipose tissue, and particularly from the umbilical cord.

Umbilical cord-derived stem cells (WJ-MSC) exhibit the following characteristics:

• Younger cells with high proliferative and regenerative capacity
• Minimal impact during extraction and minimal ethical concerns.
• When transplanted into another individual, immune rejection is less likely to occur.

For this reason, WJ-MSCs can be applied to patients unable to provide autologous cells, and hold significant promise for future clinical applications of the therapy.

Treatment approach

There are two Stem Cell Therapy methods currently under consideration.

Method of Stem Cell Transplantation into the Body

• Injeksi intravena:
  The method involves administering stem cells through blood vessels, reaching the inner ear via systemic circulation. The burden on the body is relatively small, and clinical trials are already underway.
• Injeksi lokal (injeksi tympanic, dll):
  The method involves delivering stem cells to a location closer to the inner ear through the eardrum and middle ear. This is an approach aimed at direct action, but balancing invasiveness is a challenge.
• Pengenalan bedah:
  Surgical technique for delivering stem cells directly to the inner ear. Still in the experimental stage, but applicable to severe cases.

Sekretosom Therapy

It is not the stem cells themselves, but only the beneficial substances secreted by the stem cells during cultivation (growth factors, cytokines, etc.) that are extracted and administered.

• Since no cells are transplanted, its safety is high.
• The exclusive provision of components simplifies management and minimizes the risk of adverse effects.

Animal study results have reported that the use of secretosomes enhances the protection and repair of inner ear tissue, and future clinical applications are anticipated.

How Does Stem Cell Therapy Work for Hearing?

Replenishing lost hair cells and auditory nerves.

Stem cells possess the characteristic of differentiation, enabling them to transform into various cell types. For sensorineural hearing loss, it is hoped that this differentiation can be leveraged to replenish damaged hair cells and auditory nerves in the inner ear.

For example, in an experiment where umbilical cord-derived mesenchymal stem cells (MSCs) were exposed to specific growth factors (BDNF and NT-3), it was confirmed that they differentiated into cells resembling auditory neurons.

Furthermore, when stem cells were transplanted into a mouse model for age-related hearing impairment, hair cell regeneration and hearing improvement have been reported.

The secretosome protects remaining cells and promotes repair.

Stem cells not only generate new cells but also release beneficial components (secretosomes) into their surroundings, which also serve to protect existing cells. Secretosomes contain,

• BDNF (Brain-Derived Neurotrophic Factor)
• NT-3 (Neurotrophin-3)
• IGF-1 (Insulin-like Growth Factor-1)

and other components that facilitate cell viability and repair, particularly supporting damaged hair cells and auditory nerve cells.

In animal experiments, when secretosomes were administered to models of inner ear damage induced by the anticancer drug cisplatin, it has been reported that hearing loss was attenuated and hair cell loss was reduced.

Alleviating inner ear inflammation and creating an environment for recovery.

In some cases of sensorineural hearing loss, inner ear inflammation or autoimmune reactions are involved. Excessive inflammation can accelerate tissue damage and impede hearing recovery. Stem cells exhibit immunomodulatory effects against such inflammation.

Specifically,

• In autoimmune hearing loss models, stem cell administration reduces aggressive immune cells (autoreactive T cells).
• Instead, regulatory T cells that suppress inflammation and anti-inflammatory cytokines (e.g., IL-10) are increased.

Consequently, inner ear tissue damage was attenuated, and the preservation and restoration of hearing were promoted, as demonstrated in animal experiments.

Research findings—To what extent can hearing recover?

Potential shown by Stem Cell Therapy in animal experiments

In animal studies utilizing mice and rats, Stem Cell Therapy has been repeatedly confirmed to have a beneficial effect on hearing.

• Model of noise-induced hearing loss

  When human umbilical cord-derived MSCs were transplanted into mice whose inner ears were damaged by loud noise, the decline in hearing was significantly suppressed. After transplantation, activation of genes related to immunomodulation and antioxidants was observed, and the cell death suppressive effect was also confirmed.

• Model of age-related hearing loss

  When MSCs were transplanted into aged mice, hair cells were regenerated and hearing was restored to a level close to when they were young. It is thought that the anti-inflammatory substance secreted by stem cells (apelin) also contributes to suppressing inner ear inflammation.

• Drug-induced hearing loss model

  In a model of hearing impairment induced by the anticancer drug cisplatin, by administering secretosomes derived from MSCs, hearing deterioration was prevented, and hair cell loss was also significantly reduced.

These results strongly indicate the possibility that Stem Cell Therapy renders "ear regeneration" a reality.

Visible signals from early clinical trials

Stem cell therapy in humans has also reported results, although still in its early stages.

• Treatment of adult hearing impairment with autologous bone marrow MSC (Korea)

  In a clinical trial where MSCs derived from the patients' own bone marrow were administered intravenously to patients with severe sensorineural hearing loss, no serious side effects were detected, and safety was confirmed. Furthermore, in some patients, there was a small trend of improvement in hearing test scores.

• Treatment of pediatric hearing loss with umbilical cord blood MSCs (US)

  In a trial administering cord blood-derived stem cells to 11 pediatric patients with hearing impairment, aged 6 months to 6 years, no serious adverse events occurred in any case, and the treatment could be safely administered. Following treatment, improvements in auditory brainstem response (ABR) were observed in some children, and positive effects on language development are expected.

Stem Cell Therapy Safety: An Accurate Understanding of Concerning Side Effects

Key safety findings in Stem Cell Therapy

• Immune rejection is rare.

  MSCs have the function of modulating immunity, and it is known that even when introduced into the body, strong rejection reactions are not easily triggered. Specifically, WJ-MSCs have the characteristic that their HLA (human leukocyte antigen) type is immature, making them more easily accepted even from other sources. No serious immune rejection reactions have been reported in previous animal experiments or clinical trials.

• The risk of tumorigenicity is extremely low.

  Unlike embryonic stem cells or iPS cells, MSCs are known to have a very low risk of forming tumors or teratomas. In fact, in MSC therapy conducted worldwide, there have been almost no reports of cancer occurring.

• Long-term security is also being confirmed.

  In a multi-year follow-up study on hearing-impaired patients who had undergone Stem Cell Therapy, no major problems were detected even 3 years after treatment. This indicates that MSCs remain stable in the body or naturally disappear after completing their role.

• Minimal short-term side effects

  When MSCs are administered via IV infusion, a mild fever or pain at the injection site may be observed for a very short period. Also, in local administration around the inner ear, transient dizziness or tinnitus has been reported in some cases, but all recovered naturally within a short time, and no serious complications were confirmed.

Comprehensive security evaluation

Stem Cell Therapy, particularly treatment using umbilical cord-derived MSCs, can be described as a highly safe regenerative medicine method with a low risk of rejection reactions and tumor formation.

While regenerative medicine remains a relatively nascent field, necessitating careful future observation, the data available to date suggest it possesses a more favorable safety profile compared to traditional surgical interventions or pharmacological treatments.

A Future of Restored Hearing—The Promise of Stem Cell Therapy

Sensorineural hearing loss has long been considered an "incurable hearing disorder."

Once the hair cells and auditory nerves of the inner ear are damaged, they do not regenerate. Therefore, only the remaining function can be compensated for with hearing aids or cochlear implants – a reality many patients are compelled to accept.

However, with the advent of regenerative medicine, specifically Stem Cell Therapy, the conventional understanding of treating hearing loss is undergoing a dramatic shift. Based on animal studies and preliminary clinical investigations, the potential for damaged hair cells and auditory nerves to regenerate, thereby restoring hearing, has emerged as a tangible reality.

Notably, umbilical cord-derived mesenchymal stem cells (UC-MSCs) exhibit exceptional superiority in regenerative capacity and safety, leading to mounting global expectations for their potential as a pivotal therapeutic strategy to address sensorineural hearing loss.

For individuals afflicted with sensorineural hearing loss, Stem Cell Therapy holds immense promise for the future. We sincerely hope that this promise will soon materialize, restoring the invaluable gift of hearing to countless individuals.

• Organisasi Kesehatan Dunia (WHO): Deafness and hearing loss – Lembar Fakta Organisasi Kesehatan DuniaWHO Fact Sheet on the Number of People with Hearing Impairment Worldwide and Its Impact
  Extracellular Vesicles in Inner Ear Therapies—Pathophysiological, Manufacturing, and Clinical Considerations
• Warnecke A, et al. (2021): Successful Treatment of Noise-Induced Hearing Loss by Mesenchymal Stromal Cells: An RNAseq Analysis of Protective/Repair Pathways(Research on the effectiveness of Umbilical Cord Stem Cell Therapy for noise-induced hearing loss in rats and related gene analysis)
  Frontiers | Successful Treatment of Noise-Induced Hearing Loss by Mesenchymal Stromal Cells
• Xu S, et al. (2025): Innovative treatment of age-related hearing loss using MSCs and EVs with Apelin(Research demonstrating hair cell regeneration and hearing recovery through MSC transplantation in an age-related hearing impairment mouse model, and the effectiveness of MSC-derived apelin)
  Innovative treatment of age-related hearing loss using MSCs and EVs with Apelin
• Tsai S-CS, et al. (2022): The intravenous administration of skin-derived mesenchymal stem cells ameliorates hearing loss and preserves cochlear hair cells in cisplatin-injected miceA study showing that intravenous administration of skin-derived MSCs protects hearing in mice with cisplatin-induced hearing loss and prevents cochlear hair cell loss.
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• Zhou Y, et al. (2011): The therapeutic efficacy of human adipose tissue-derived mesenchymal stem cells on experimental autoimmune hearing loss in mice(Research showing that human adipose-derived MSCs improve hearing in mouse models of autoimmune hearing loss, suppress inflammatory T cells, and increase regulatory T cells)
  The therapeutic efficacy of human adipose tissue-derived mesenchymal stem cells
• Lee HS, et al. (2018): Clinical Safety and Efficacy of Autologous Bone Marrow-Derived Mesenchymal Stem Cell Transplantation in Sensorineural Hearing Loss Patients(Preliminary clinical trial of autologous bone marrow MSC therapy in patients with severe sensorineural hearing loss, safety confirmed and there are signs of hearing improvement in some patients)
  Application of Mesenchymal Stem Cell Therapy and Inner Ear Regeneration
• Baumgartner LS, et al. (2018): Intravenous autologous cord blood therapy for pediatric sensorineural hearing lossA trial of umbilical cord blood stem cell therapy in 11 pediatric patients with hearing loss, aged 6 months to 6 years, was safely performed, and improvement in ABR thresholds was reported in about half of them.
  Stem cell therapy in sensorineural hearing loss – The Egyptian Journal of Otolaryngology
• Mady OM, et al. (2023): Stem cell therapy in sensorineural hearing loss: a systematic reviewA systematic review summarizing the latest research on Stem Cell Therapy for sensorineural hearing loss. It concludes that 90% of animal trials showed hearing improvement, and clinical reports demonstrate safety and promising results.
  Stem Cell Therapy in Sensorineural Hearing Loss: A Systematic Review