New study: the role of Mesenchymal Stromal Cells and Apoptotic Bodies in immune regulation

The role of Mesenchymal Stromal Cells and Apoptotic Bodies in immune regulation

Mesenchymal stromal cells (MSCs) are special cells found in many parts of the body that have shown promise in treating various diseases. Like all cells, MSCs release tiny particles called extracellular vesicles, which come in different sizes and shapes. Interestingly, even when MSCs start to die, they continue to release these vesicles, called apoptotic bodies (ApoBDs) – which might still have beneficial effects, especially on regulating the immune system.

Research has shown that MSC-derived ApoBDs can help regulate the immune system, however they have not been studied as much as smaller extracellular vesicles. To fill in the gap, our team at Galway conducted a study to explore the therapeutic potential of large and small ApoBDs.

By understanding the immune-modulating properties of these vesicles, Restore Vision hopes to identify the best candidates for new treatments for immune-related diseases that affect the eye.

What was the purpose of the study?

This study aimed to explore the therapeutic potential of two types of apoptotic bodies (ApoBDs)—large and small—released by mesenchymal stromal cells (MSCs) when they undergo cell death. To trigger this process, the researchers used a chemical called staurosporine to induce cell death in MSCs. They then compared the effects of large ApoBDs (about 700 nm in size) and small ApoBDs (about 500 nm) on immune cells through a series of experiments in the lab.

What were the main findings?

The study found that both large and small ApoBDs were able to suppress T-cell activity. This is crucial for effective immunotherapy since overactive T-cells contribute to many inflammatory diseases. While both types of ApoBDs inhibited T-cell proliferation, large ApoBDs proved to be more effective at doing so.

Additionally, large ApoBDs helped shift macrophages – another type of immune cell – from a pro-inflammatory state to one that reduces inflammation. They also entered macrophages more easily, suggesting that large ApoBDs could be even more potent in delivering their beneficial effects.

Importantly, neither large nor small ApoBDs showed any signs of toxicity, indicating they could be safe options for future therapeutic application.

What are the main implications?

These findings suggest that staurosporine-induced ApoBDs are non-toxic and have strong immunomodulatory potential. Large ApoBDs appear to be more effective than small ones at suppressing T-cells and promoting anti-inflammatory macrophages. This suggests that large ApoBDs could be a promising alternative to MSC-based therapies in treating immune-related diseases.

While the results of this study are promising, the research on ApoBD is still in early days and more studies are needed to explore how ApoBDs work in pre-clinical models and clinical settings. Additionally, understanding how these vesicles interact with different immune cells could help optimise their use for therapeutic applications.