Treatment for Age-Related Hearing Loss: The Role of MSCs and Extracellular Vesicles

As we age, hearing loss becomes more common—and frustrating. It’s not just about turning up the volume; it’s about tiny, delicate cells in our ears that get damaged and don’t grow back. Scientists are now exploring how stem cells and their “messenger bubbles” (called EVs) might actually help the body repair itself. This could mean real healing, not just hearing aids.

In a recent study conducted by Xu et al., published in Cell Biology and Toxicology (2025), researchers investigated the potential of mesenchymal stem cells (MSCs) and their extracellular vesicles (EVs) as a treatment for age-related hearing loss (ARHL). ARHL is a common condition in older adults, leading to permanent hearing impairment due to the loss of sensory hair cells in the cochlea. Currently, there are limited options to address the underlying causes of this condition, making the search for effective therapies a priority.

The study provides evidence that MSCs, when combined with Apelin-containing EVs, can support the regeneration of cochlear hair cells, potentially restoring hearing function. This blog summarizes the key findings from this research and their implications for ARHL treatment.

What is Apelin?

Apelin is a peptide hormone that plays a role in various physiological processes, including regulating blood pressure, promoting angiogenesis (formation of new blood vessels), and modulating inflammation. Apelin binds to the APJ receptor, which is expressed in various tissues, including the brain, heart, and cochlea.

In the context of this study, Apelin is delivered via EVs to macrophages (a type of immune cell) in the cochlea. It helps regulate the immune response by promoting M2 macrophage polarization, which is associated with anti-inflammatory effects and tissue repair. This action of Apelin in MSC-derived EVs contributes to the regeneration of hair cells in the cochlea, ultimately supporting the restoration of hearing.

Key Findings

The research demonstrated that MSCs can differentiate into inner ear cells, particularly hair cells, which are essential for hearing. This differentiation is facilitated by the delivery of Apelin via MSC-derived EVs, which promotes macrophage polarization toward the M2 phenotype (tissue-healing immune cells). M2 macrophages are associated with tissue repair, playing a critical role in reducing the inflammation that often accompanies ARHL.

In vitro experiments showed reduced inflammation and improved health of hair cells, while in vivo experiments in aging mice led to hair cell regeneration and restored hearing. These results suggest that MSCs and EVs could offer a new approach to managing ARHL.

MSCs and Hair Cell Regeneration

Hair cells in the cochlea are responsible for detecting sound and transmitting signals to the brain. Their loss due to aging is a primary cause of hearing impairment. However, mammals, including humans, cannot naturally regenerate these cells.

The study showed that MSCs have the potential to differentiate into auditory cells, including hair cells, Deiter cells, and pillar cells, in the cochlea. This process is supported by the presence of Apelin in MSC-derived EVs, which enhances macrophage polarization and helps regulate inflammation in the cochlea.

Both in vitro and in vivo experiments confirmed that MSCs transplanted into aging mice successfully regenerated hair cells and improved auditory function. These findings suggest that MSCs could be a viable approach for treating hearing loss in individuals with ARHL.

Role of Extracellular Vesicles (EVs)

EVs (extracellular vesicles) are small, membrane-bound particles released by cells that carry bioactive molecules such as proteins, lipids, and RNA, and play a key role in intercellular communication.

The study highlighted the role of MSC-derived EVs in promoting hair cell regeneration. Apelin, a peptide hormone found in these EVs, helps modulate inflammation and supports the polarization of macrophages toward the M2 phenotype. M2 macrophages are involved in tissue repair and regeneration, which is crucial for addressing the inflammation typically present in ARHL.

The researchers demonstrated that EVs could deliver Apelin directly to macrophages in the cochlea, shifting the macrophages from a pro-inflammatory M1 state to a tissue-repairing M2 state. This shift is important for reducing inflammation and promoting the healing of cochlear tissues, facilitating the regeneration of hair cells.

Impact on Auditory Function

The study also showed a significant improvement in hearing function following MSC transplantation and EV treatment. Auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAE) tests indicated improved hearing thresholds, suggesting restored hearing function.

Additionally, key proteins involved in cochlear function, such as Cx26 and Na–K ATPase, were upregulated, providing molecular evidence for the regenerative effects of MSCs and EVs.

What’s Next?

While this study was conducted in mice, the implications for human hearing loss are exciting. Could we one day use MSCs or EV-based treatments in the clinic to help people hear again? Further research and human clinical trials will be needed—but this work lays a promising foundation.

Conclusion

This study demonstrates the potential of MSCs and their EVs as a treatment for ARHL. By promoting hair cell regeneration and reducing inflammation, MSCs and EVs offer a promising approach to addressing the underlying causes of hearing loss in aging individuals.

By leveraging MSCs and EVs, it may be possible to not only manage the symptoms of ARHL but also address the cellular damage that causes the condition—offering a new and hopeful avenue for hearing restoration.

Glossary for New Readers

• MSC (Mesenchymal Stem Cells) – Special cells that can become bone, fat, or cartilage and help reduce inflammation.
• EV (Extracellular Vesicle) – Tiny bubble-like structures that cells use to send signals and helpful materials to other cells.
• Apelin – A hormone that reduces inflammation and supports tissue healing.
• Macrophages (M1/M2) – Immune cells that can either fight threats (M1) or help heal tissue (M2).
• Hair Cells – Specialized cells in your ear that help detect sound and send it to your brain.

Scaling Up for Real-World Impact

Did you know you can scale up MSC production and enhance EV output using microcarriers?
When grown in 3D environments like bioreactors, MSCs expand more efficiently on microcarrier surfaces. This leads to more cells, greater EV yield, and broader therapeutic potential—an approach that aligns with the goals of studies like this one.