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This is a simplified version of how exosomes are formed within a cell. — Photos: Wikimedia Commons

This stealthy biological carrier holds promise for regenerative medicine

Regenerative medicine is expanding its toolkit beyond stem cells, incorporating exosomes for tissue repair, gene therapy for genetic disorders, and biocompatible materials for scaffolding.

This evolution reflects a promising growth in strategies for restoring damaged tissues and organs. Exosomes, in particular, have become a focal point in cellular therapy, promising to revolutionise treatment methodologies across various diseases.

Cellular therapy – a subset of regenerative medicine – involves administering living cells to repair or modify the function of injured or diseased tissues and organs. This approach has traditionally centred on using whole cells – predominantly stem cells, which are known for their regenerative capabilities. However, the emergence of exosomes has shifted the focus to these tiny particles.

An intercellular communicator

Exosomes are small extracellular vesicles, typically measuring between 30-150 micrometres in diameter. They are secreted ubiquitously by various cell types. Once regarded as mere cellular detritus, exosomes have gained recognition for their crucial role in intercellular communication.

These vesicles are laden with an array of biological molecules, including proteins, lipids, various forms of RNA (such as messenger RNA and microRNA), and even DNA. This molecular diversity enables them to transfer genetic and protein-based information from one cell to another, significantly influencing the recipient cells’ functions.

Scientific data show that exosomes are involved in numerous physiological processes, from immune responses to tissue repair and regeneration. Exosomes offer a unique advantage: they encapsulate the regenerative properties of their parent cells, but without the complexities and risks often associated with direct cell therapies.

This includes reduced risk of immune rejection, and the potential for more controlled and targeted therapeutic effects. One of the key scientific revelations about exosomes is their ability to cross biological barriers, such as the blood-brain barrier, which makes them highly promising for treating neurological disorders.

Studies have demonstrated that exosomes can effectively deliver therapeutic agents to the brain, opening new avenues for treating conditions like dementia (including Alzheimer’s disease), fine tremors and multiple sclerosis. Furthermore, the role of exosomes in cancer has been a significant area of interest.

Research has indicated that tumour-derived exosomes can modulate the tumour microenvironment, influence metastasis (spread of cancerous cells to other parts of the body), and even play a role in drug resistance.

This understanding has paved the way for using exosomes as biomarkers for early cancer detection and as vehicles for delivering targeted cancer therapies, potentially reducing the adverse effects of traditional chemotherapy.

As a therapeutic agent

Exosomes offer several unique advantages as therapeutic agents, primarily owing to their biocompatibility and natural origin, including:

Minimised risk of immune rejection

Due to their endogenous origin (within the body), exosomes are less likely to evoke an immune response – a significant advantage over other therapeutic delivery systems. This attribute is critical in transplant medicine and cell-based therapies, where immune rejection poses a substantial risk.

A study in the scientific journal ACS Nano demonstrated that exosomes derived from dendritic cells could induce immune tolerance, suggesting their potential in reducing organ transplant rejection.

Ability to evade immune surveillance

Another advantage is their small size and inherent biological composition, which allows them to escape detection by the body’s immune system. This feature facilitates the delivery of therapeutic agents to target cells without eliciting an immune response.

Research published in the scientific journal Biomaterials showed that exosomes could successfully evade phagocytosis (ingestion by a cell’s membrane), thus enhancing their longevity and efficacy as drug delivery vehicles.

Targeted delivery to specific cells

Perhaps one of the most significant advantages of exosomes is their inherent ability to target specific cells or tissues. This capability is attributed to their surface molecules, which can be engineered to recognise and bind to specific cell types.

For instance, a study in the scientific journal Nature Biotechnology demonstrated that exosomes could be engineered to deliver drugs specifically to cancer cells, significantly enhancing the efficacy of cancer therapy.

In regenerative medicine

Exosomes are emerging as a significant tool in regenerative medicine due to their ability to facilitate tissue repair and regeneration. This potential stems from their role in cell-to-cell communication, carrying and delivering bioactive molecules that can influence the behaviour of recipient cells. They can potentially play a role in instances like:

Tissue repair and regeneration

Exosomes can modulate various cellular processes crucial for tissue repair, including promoting cell proliferation, migration and angiogenesis (formation of new blood vessels).

A study published in the medical journal Stem Cells Translational Medicine demonstrated that exosomes derived from mesenchymal stem cells (MSCs) could enhance wound healing. These exosomes were found to promote collagen synthesis and angiogenesis, thus accelerating wound closure.

Degenerative diseases

In the context of degenerative diseases, exosomes show promise in neurodegeneration (degeneration of nerve cells) and osteoarthritis.

For instance, a study in the Journal of Extracellular Vesicles showed that MSC-derived exosomes could promote neurogenesis (growth of nerve cells) and provide neuroprotection in models of Parkinson’s disease.

The exosomes were found to contain neurotrophic factors that support neuronal growth and survival. In osteoarthritis, exosomes have been shown to have anti-inflammatory and chondroprotective (cartilage-protecting) effects.

Research in the medical journal Osteoarthritis and Cartilage indicated that exosomes from MSCs could reduce cartilage degradation and inflammation in osteoarthritis models, suggesting their potential as a therapeutic agent.

Organ repair

Exosomes have also been studied for their role in organ repair, particularly in cardiac (heart) and liver injuries. A publication in the medical journal Circulation Research highlighted that exosomes from cardiac stem cells could promote cardiac repair following a heart attack.

These exosomes were found to carry cardiac-specific microRNAs that can modulate cell survival and proliferation pathways. Similarly, in liver injury, a study in the Journal of Hepatology indicated that exosomes could facilitate liver regeneration.

The exosomes were observed to carry specific microRNAs and proteins that help in reducing inflammation and promoting liver cell proliferation.

Chronic wound healing

Chronic wounds, such as diabetic ulcers, represent a significant challenge in clinical management. Exosomes are being explored for their potential in improving wound healing in such conditions.

Research in the journal Advanced Science demonstrated that exosomes could enhance wound healing in diabetic models by promoting angiogenesis and modulating the immune response at the wound site.

Future hope

In summary, exosomes are emerging as a significant innovation in medical science. Their natural compatibility and targeted delivery capabilities mark them as a revolutionary method for drug delivery and disease management.

Their role in the realm of regenerative medicine is equally transformative, offering a means to influence tissue repair for chronic wounds and organ injuries, and in treating degenerative diseases.

As research progresses, the utilisation of exosomes could revolutionise treatment strategies for a host of complex medical conditions and play an increasingly important role in the development of regenerative therapies.

This offers hope for conditions currently challenging to treat, thus signalling a new era in therapeutic approaches.

By Datuk Dr Nor Ashikin Mokhtar
Published in Star Newspaper, 11 Mar 2024

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