Unless you’re a molecular biologist, you’d be forgiven for not knowing what an exosome is. Nonetheless, if you have an interest in optimizing your health – particularly if you or a loved one suffers from a chronic illness like cancer or Alzheimer’s disease – you’ll want to learn about them.

Image source: Advances in Experimental Medicine and Biology

Exosomes have vastly underrated implications for anti-aging healthcare. A growing body of literature shows that exosomes often contribute to the development of viral pathogenicity, immune/autoimmune responses, cardiovascular disease, central nervous system conditions, and cancer progression, among other disease processes.

As we’ll document here, exosomes via targeted therapy may also play a starring role in the treatment and prevention of these devastating diseases.

Here, we’ll discuss what exosomes are, their recently discovered function in human physiology, and, most importantly for patients, their revolutionary potential healthcare applications.

What Are Exosomes?

Exosomes are a unique type of “extracellular vesicle” (EV), a term indicating that they exist outside and independent of the cell structure.

They are typically produced by eukaryotic cells (the biological term for cells with a clearly defined nucleus) and subsequently released into the bloodstream or tissues. Depending on where they come from, exosomes can contain multiple molecular constituents donated by their origin cell, including ribonucleic acid (RNA) and proteins.

One of the exosome’s primary functions is to ferry these RNA messages and proteins between cells, often traversing large distances. When exosomes then interface with their recipient cells, they alter their function either for the better or for the worse.

Historically, until relatively recently, exosomes had been largely neglected as an area of research interest for scientists, but that oversight is changing rapidly as scientists discover greater clinical utility and applications for these unique EVs. Later on, we’ll discover the present-day and future medical uses for exosomes.

Previously, biologists’ working assumption was that exosomes were likely just molecular “trash” – pieces of biological debris that cells ejected when they didn’t need them any longer. Now, however, on the heels of recent scientific inquiry, we understand that exosomes perform important, and often critical, physiological functions – for example, the previously described activity of transferring mRNA genetic material between cells.

Exosomes are present nearly everywhere in the human body. They have been found in multiple biological fluids and tissues, including in the urine, blood, extracellular tissue matrix, and cerebrospinal fluid.

What Are The Physical Properties of Exosomes?

Exosomes’ average diameter is roughly 100 nanometers (much smaller in size than human cells, approximately equivalent in mass to a lipoprotein). They range in size from as small as 30 nm and as large as 150 nm.

Their constituent parts are made up of proteins, lipids, amino acids, nucleic acids, and metabolites (taken from the origin cell).

Due to their small size, detecting exosomes with conventional imaging techniques is difficult. The Western blot and mass spectrometry tests may be useful for detecting proteins in exosomes’ total populations. Clinicians can also separate exosomes from the fluids or tissues that they’re embedded in by a labor-intensive process called differential ultracentrifugation.

Researchers are diligently developing new methods of exosome isolation and extraction to scale up their clinical viability.

Given their ability to traverse large distances in the body, as well as their carrying capacity for DNA, RNA, and various lipids, proteins, and amino acids, exosomes have enormous clinical upside in terms of use as novel therapeutics.

Coming up, we’ll detail the innovative ways by which researchers hope to put exosomes to work treating difficult and debilitating chronic illnesses.

Exosomes are a powerful diagnostic tool

As we touched on previously, exosomes convey genetic material (including RNA and even double-strand DNA) that regulates gene expression. Accordingly, when things go wrong, they’ve been shown to contain pathological materials that contribute to the development of chronic illnesses:

“The vesicles are implicated in spreading diseases, including cancer, and metabolic conditions, like diabetes and obesity. A recent study even points to exosomes as a culprit for distributing amyloid-β, the plaque-forming protein that accumulates in the brains of people with Alzheimer’s disease.”

Optimal treatment for any disease – from COVID-19 to cancer to diabetes – hinges on detecting it as early as possible and taking immediate corrective action. That’s why researchers are so interested in continually developing more accurate diagnostic processes to identify biomarkers indicative of illness, including exosomes.

Although cells release exosomes under normal physiological conditions, exosomes often carry such biomarkers for several diseases:

“Over the past few years, numerous studies have demonstrated that exosomes contain nucleic acids and proteins implicated in cancer as well as neurodegenerative, metabolic, infectious, and other diseases.”

As an example, for the purpose of monitoring cancer progression as well as the efficacy of anti-cancer therapeutics, exosomes have demonstrated immense clinical utility:

“Exosome-based liquid biopsy highlights their potential utility in diagnosis and determining the prognosis of patients with cancer and other diseases. Disease progression and response to therapy may also be ascertained by a multicomponent analysis of exosomes.”

The upside is that, if a current cancer treatment regimen isn’t working as intended, the oncologist (cancer doctor) can modulate the therapy protocol and hopefully achieve more optimal results.

Combined with the increasing technological ease of isolating and analyzing exosomes from fluids and tissues, exosome testing is rapidly evolving into an accurate, cost-effective method to diagnose many of the most common illnesses plaguing patients.

Exosomes as breakthrough therapeutics

As with many features of human biology, exosomes are a double-edged physiological sword. As we’ve documented, they can contribute to (and even potentially cause) multiple diseases. But, under the right circumstances, they can also act as healing agents.

Exosomes may prove to exert positive clinical effects when applied judiciously. Scientists are particularly interested in exploring their usefulness for curing or preventing diseases that currently have a poor prognosis with limited effective treatment options:

“If exosomes can so easily carry molecules that spread disease, scientists began thinking they might be useful to carry molecules that stop disease.”

Exosomes as novel agents for drug delivery

We’ve established already that exosomes deliver messages to cells by way of the genetic material they carry. Given that role, they have  untapped clinical utility for delivering therapeutics through that same mechanism:

“[Scientists] are manipulating exosomes to solve drug delivery problems for a dizzying array of therapies: small molecules, RNA therapies, proteins, viral gene therapy, and even CRISPR gene-editing tools. Studies in cells and animals suggest that exosomes could be the gift wrapping for them all.”

DNA is often referred to as the “building block of life” – the blueprint for how the body functions and repairs itself following illness or injury. Gaining the ability to efficiently manipulate DNA without damaging the entire genome would be a game-changer for hundreds of millions of patients worldwide battling currently untreatable health conditions.

Many clinicians and doctors on the cutting edge of anti-aging research herald CRISPR (an acronym for “clustered regularly interspaced short palindromic repeats”) gene editing as the future of medicine. According to studies by leading research institutes worldwide, CRISPR has the potential to prevent, treat, and possibly reverse the negative health impacts of chronic illnesses.

Health conditions that result, in whole or in part, from defective DNA are termed “congenital.” Several diseases – including a slew of cancers, neurodegenerative conditions, and others – are associated with DNA damage and defective responses to that damage:

“Cellular DNA damage is implicated in the aetiology and progression of many different types of human disorders and diseases… DNA damage is also implicated in the development of other prevalent human diseases ranging from neurodegenerative disorders such as Alzheimer’s disease to chronic obstructive pulmonary disease (COPD).”

As of 2022, there is no reliable, affordable, proven-safe therapeutic intervention to repair a dysfunctional genome, leaving patients with these conditions at a loss. That’s where CRISPR and, potentially, exosomes come into play.

When a chronic health condition’s root cause is damaged DNA or defective genetic expression, CRISPR enables healthcare providers to mechanically alter the genome in beneficial ways using a precision pair of metaphorical gene “scissors” that disrupt pathological DNA sequences. They can even conceivably replace damaged DNA with healthy replacements:

“CRISPR is a powerful tool for editing genomes, meaning it allows researchers to easily alter DNA sequences and modify gene function. It has many potential applications, including correcting genetic defects, treating and preventing the spread of diseases.”

CRISPR is arguably the most promising form of genetic manipulation in the rapidly advancing field of genomic medicine. However, the dilemma is how best to deliver these gene-editing materials to the tissues and cells that need them.

One of the main impediments to turning CRISPR from theory into practice is the difficulty of delivering the gene-altering materials in durable packaging without encountering immune system resistance. Thus the potential synergistic activity of CRISPR and exosomes emerges:

“Non-autologous exosomes can encapsulate CRISPR/Cas9 plasmid DNA via commonly available transfection reagents and can be delivered to recipient cancer cells to induce targeted gene deletion.”

Source: University of Georgia

Researchers studying exosome-mediated delivery of CRISPR technology have demonstrated proof of concept in using the technology to treat pancreatic cancer.

There are more advantages to using exosomes as drug delivery agents. Exosomes have the unique capacity to cross the blood-brain barrier – the biggest obstacle to designing therapeutics that effectively reach the brain. This is relevant to the treatment of complex neurological conditions such as Alzheimer’s disease, brain cancer, or traumatic injury

Exosomes as an alternative therapy to stem cell therapy using mesenchymal stem cells (MSCs)

Stem cell therapy is a rapidly evolving field of regenerative medicine.

Stem cells occur naturally in the human body. They offer the unique capacity to develop into specialized cells like brain cells, heart cells, liver cells, and others – which, in theory, could be used to regenerate damaged or diseased organs and tissues. They are also proposed for the purpose of engineering entirely new organs in laboratory settings for transplantation.

Source: Science Chronicle

However, stem cells’ clinical utility is limited. Thus far, human experiments using stem cell therapy have yielded mixed and largely disappointing results.

There are also ethical issues involved in stem cell therapy because most of the stem cells currently used in clinical research are sourced from human embryos, which leads to claims among critics that using them for scientic pursuits is a violation of human rights.

Exosomes’ limited efficacy, as well as the ethical dispute over their use, is why researchers have increasingly looked towards exosomes as an alternative to stem cells to achieve the same results. They act in the same way as stem cells but with greater accuracy and fewer logistical challenges:

“Exosomes, which are secreted by MSCs through paracrine signalling, not only have the same effects as MSCs, but they also have the advantages of targeted delivery, low immunogenicity, and high repairability.”

The future of exosomes is bright

We’ve come a long way in the last few decades from the initial discovery of exosomes in 1983.

Scientists are just beginning to scratch the surface in terms of what healthcare solutions exosomes might offer to solve intractable health issues.

This instructive Ted Talk highlights the emerging potential therapeutic uses for exosomes as the science behind them rapidly develops:

https://youtu.be/NQeY_oIMNII

The main benefit of utilizing exosomes as novel diagnostic and therapeutic tools is their ability to convey genetic information and other potential therapeutic materials throughout the bloodstream and into target tissues and organs. Critically, exogenous exosomes don’t usually trigger an immune response because they are naturally-occurring features of human biology, and are therefore unlikely to encounter any immune system challenges common in other current therapeutic interventions.

With the development of more efficient production methods and ways to analyze exosome activity in vivo, their potential clinical applications will continue to multiply.