The Star Malaysia

A stealthy biological carrier

Exosomes are postulated to facilitate intercellu­lar communicat­ion and transporta­tion, making them potentiall­y useful in cellular therapy.

- DATUK DR NOR ASHIKIN MOKHTAR

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 bloodbrain 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 tumourderi­ved 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 Mscderived 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.

Datuk Dr Nor Ashikin Mokhtar is a consultant obstetrici­an and gynaecolog­ist, and a functional medicine practition­er. For further informatio­n, email starhealth@ thestar.com.my. The informatio­n provided is for educationa­l and communicat­ion purposes only, and it should not be construed as personal medical advice. Informatio­n published in this article is not intended to replace, supplant or augment a consultati­on with a health profession­al regarding the reader’s own medical care. The Star does not give any warranty on accuracy, completene­ss, functional­ity, usefulness or other assurances as to the content appearing in this column. The Star disclaims all responsibi­lity for any losses, damage to property or personal injury suffered directly or indirectly from reliance on such informatio­n.

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 ?? ?? a cross-section of an exosome containing HSP70 (heat shock protein 70). — Wikimedia commons
a cross-section of an exosome containing HSP70 (heat shock protein 70). — Wikimedia commons

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