Injectable Gel Boosts Stem Cell Survival for Swallowing Disorders | McGill University Research

A new approach to stem cell therapy, involving an injectable gel, offers potential for repairing damaged swallowing muscles, a condition affecting millions worldwide. Researchers at McGill University and Kyoto University have developed a method that significantly improves stem cell survival after injection, a longstanding challenge in regenerative medicine. The findings, published in Biomaterials, suggest a minimally invasive option could one day restore swallowing function for individuals with limited treatment options.

The Challenge of Swallowing Disorders

Difficulty swallowing, known as dysphagia, impacts approximately eight percent of the global population. This can stem from a variety of causes, including stroke, the side effects of radiation therapy for head and neck cancer, and the natural aging process. The consequences of dysphagia can be severe, ranging from malnutrition and dehydration to aspiration pneumonia – a dangerous lung infection caused by food or liquid entering the airway. Current treatments often involve rehabilitation exercises or, in more serious cases, surgery.

Stem cell therapy has emerged as a promising avenue for muscle repair, including the muscles crucial for swallowing. However, a major hurdle has been the poor survival rate of transplanted cells in an injured environment. Many cells die quickly after injection, limiting the therapy’s effectiveness.

Nanogel ‘Scaffolding’ Improves Cell Viability

To overcome this challenge, the research team focused on creating a more supportive environment for the stem cells. Previous attempts to cluster stem cells into spheroids – three-dimensional cell clusters – faced a problem: larger spheroids often develop a necrotic core, where cells die due to lack of oxygen and nutrients.

The innovative solution involved integrating biodegradable nanogels into the stem cell spheroids. These nanogels, synthesized from a modified carbohydrate called pullulan, act as a microscopic scaffolding. “The gel fragments act like scaffolding. They create pathways that give the cluster breathing room, allowing oxygen and nutrients to circulate while keeping it intact,” explained Dr. Hideaki Okuyama, a visiting researcher at Kyoto University’s Department of Otorhinolaryngology-Head and Neck Surgery and first author of the study. Dr. Okuyama previously trained as a postdoctoral fellow at McGill under the guidance of senior author Nicole Li-Jessen.

The team mixed the nanogel fragments with stem cells derived from connective tissue to create these hybrid spheroids. Lab tests demonstrated a significant improvement in cell viability. After one week, the hybrid clusters were approximately 5.6 times more viable than standard clusters. They released higher levels of substances known to promote tissue repair.

Positive Results in Animal Models

The effectiveness of this approach was further tested in a rat model. A single injection of the nanogel-integrated stem cell spheroids resulted in greater stem cell retention and a nine-percent improvement in swallowing-muscle activity after three weeks. This suggests the gel not only enhances cell survival but also contributes to functional recovery.

Gel’s Safety Profile and Prior Testing

Notably, the biodegradable gel used in this study isn’t entirely new to clinical investigation. According to Nicole Li-Jessen, Associate Professor in McGill’s School of Communication Sciences and Disorders, the gel has already undergone Phase I and II clinical testing in Japan as part of an experimental cancer vaccine. This prior testing provides some reassurance regarding its safety profile, although further evaluation is always necessary when applying a material to a new therapeutic context.

Expanding the Potential Applications

While the initial focus is on swallowing disorders, researchers are exploring whether this nanogel-based approach could be adapted to treat other conditions involving muscle damage or loss. Potential applications include vocal cord injury, age-related muscle loss (sarcopenia), and even muscular dystrophy. The versatility of the nanogel scaffolding could make it a valuable tool in a wide range of regenerative medicine therapies.

Ongoing Research and Future Directions

The research team is currently investigating the long-term durability of the nanogel and its effects on tissue regeneration. Further studies are needed to fully understand the mechanisms by which the nanogel enhances stem cell function and to optimize the delivery method for different muscle groups.

The collaborative partnership between McGill University and Kyoto University, combining expertise in biomedical engineering, voice and swallowing science, and nanogel chemistry, has been instrumental in this breakthrough. This research was supported by funding from the Natural Sciences and Engineering Research Council of Canada, the National Institutes of Health, the McGill Regenerative Medicine Network, and the Society for Promotion of International Oto-Rhino-Laryngology.

The development of this injectable gel represents a significant step forward in stem cell therapy for swallowing disorders and holds promise for improving the quality of life for individuals affected by these debilitating conditions. As research progresses, it will be crucial to carefully evaluate the long-term safety and efficacy of this approach through rigorous clinical trials.