Exosomes (or extra cellular vesicles) are a new way to treat medical conditions including health span related medical problems. Exosomes are showing a great deal of promise in the Biotech industry as the future of regenerative medicine.
What Are Exosomes?
Exosomes are tiny packages of biomolecules released by cells1. They range between 40 and 200 nanometres in diameter, around 1000 times smaller than the width of a human hair. The biomolecules they contain including ribonucleic acid (RNA), lipids and proteins.
Exosomes are found across the natural world, including in people, other animals and plants. Their ubiquity reflects the essential role they play in cellular communication and life.
Many types of cells release exosomes, including muscle cells, brain cells, immune cells, epithelial cells, tumour cells and stem cells. Exosomes are found in virtually every biofluid, including blood, milk and saliva. Each exosome’s content depends upon the type of cell that released it and the status of that cell.
Exosomes travel freely around the body, their tiny size ensuring they can penetrate deep into the tissues and across the blood-brain barrier (BBB). They are often tagged for uptake by a specific cell type, which can be far from the cell that produced it.
Exosomes are more than just status updates – the sections of RNA they enclose and deliver contain genetic instruction that can reprogram the recipient cell’s behaviour.
Exosomes: The Body’s Master Communicators
The human body is a complex community of around 38 trillion cells of more than 200 distinct types. Like any diverse society, good communication is the key to collective success.
In the body, cell to cell communication is critical to health and wellbeing. For example, the complex human immune system uses multi-level communication to coordinate an attack on an infecting invader while limiting damage to the body’s cells and tissue. The benefits of exercise are from cross-talk between cells and different parts of our body.
Exosomes are one critical way by which our cells communicate and support each other. More than simple messages, exosomes are often more like care packages: nanoscale parcels of essential biomolecules and messages together.
The more research that is done on exosomes, the bigger the role we discover that they play in human health and aging – and the greater the role it seems exosomes could play as a regenerative medicine2.
Exosomes: A Medical Marvel Within Our Own Body
As we age, the balance of natural exosomes found circulating in the body changes; the number of inflammatory vesicles rises, while the number of regenerative exosomes declines.
Boosting the body’s regenerative exosomes back up to the level we enjoyed in our youth might prove to be a way to tackle age-related disease and declining health3.
Research has shown that exosomes taken from stem cells can treat a range of medical problems – when tested in animal models of human disease.
For example, exosomes from stem cells have been shown to improve wound healing, post-stroke rehabilitation and acute spinal cord injury.
Stem Cells or Exosomes from Stems Cells as a Drug
For the past decade or more, there has been a lot of buzz around the therapeutic potential of stem cells. These regenerative cells were thought to be capable of replacing diseased cells. It has now become clear that what the stem cells release – rather than the cells themselves – are the real source of health benefit.
Exosomes have been shown to be the essential output from stem cells. The cargo of RNA, lipids and proteins the exosomes carry activate self-repair mechanisms in recipient tissues.
Treating patients with regenerative exosomes isolated from stem cells, or other cell populations have the potential to be considerably less expensive, simpler and safer than treating them with live cells.
Regenerative Exosomes and Extended Health Span
Although conventional medicine has extended human lifespan, it has not extended our health span – the number of years that we spend active and well4. Medical conditions that limit our health span range from Alzheimer’s disease to heart disease to arthritis.
Exosomes have a multifaceted impact on health and wellbeing, with the potential to not just treat the symptoms of a disease, but to fix the underlying cause and extend the health span.
Exosomes can keep the immune system working as it should. Exosomes taken up by immune cells can modulate an overactive immune system. Inflammation – an activated immune system – is beneficial when we are fighting off an infection.
But as we age, chronic inflammation can set in, which has been implicated in many age-related diseases and autoimmune diseases such as multiple sclerosis (MS) and rheumatoid arthritis (RA). Exosomes from stem cells have immunosuppressive, anti-inflammatory effects. Through these mechanisms, exosomes could have body-wide effects that might stave off age-related incapacity and disease5.
Exosomes can also have direct impacts in aged, damaged or diseased tissue. Exosomes from adult stem cells and some other cells deliver signals to cells that promote cell proliferation and tissue growth.
For example, exosome uptake has been shown to reduce programmed cell death (apoptosis, see image below), favouring cell retention and cell division leading to tissue repair6.
Exosomes can also deliver the building blocks the cell requires to divide and regenerate tissue. Exosomes have an outer membrane made of double-layer lipids and contain a cargo of amino acids. Cells primed to divide and proliferate can consummate the action with these essential cell building blocks delivered by exosomes.
Exosomes can deliver the anti-inflammatory signalling, pro-regeneration messaging and the building blocks required for healing – an ideal combination for healing and regeneration in our bodies.
Custom Exosomes for more Targeted Jobs
The ease with which exosomes traverse the body to deliver their cargo has caught the eye of researchers looking for ways to selectively target particular cells, tissue or organs. That would focus the treatment effect on specific cell types to address a patient’s particular medical problem.
One way to harness custom exosomes is to target them to selective cell types, such as cardiac muscle cells, by attaching certain molecules to the outside of the exosomes. Researchers have already shown that exosomes can selectively deliver paclitaxel (Taxol) to lung cancer cells7.
Another way to customise exosomes is to load them up with a drug as a way to access parts of the body that are otherwise difficult for drugs to reach – including delivering drugs into the brain across the blood-brain barrier.
Combining these two approaches enables the targeted delivery of drugs to selected cells. For example, delivering a drug selectively to brain cells and avoiding side effects on other cells.
Exosomes As a New Form of Regenerative Medicine
Exosomes are a new form of regenerative medicine with emerging potential to treat a range of medical conditions affecting the health span of millions of people.
1 Lerner, T., et al. Applying Extracellular vesicles based therapeutics in clinical trials – an ISEV position paper. Journal of Extracellular Vesicles 4, 30087 (2015)
2Phinney, D. G. & Pittenger, M. F. Concise Review: MSC-Derived Exosomes for Cell-Free Therapy. Stem Cells 35, 851 (2017)
3 Eitan, E. et al. Age-Related Changes in Plasma Extracellular Veiscle Characteristics and Internalization by Leukocytes. Scientific Reports 7, 1342 (2017)
5 Safdar, A., Saleem, A. & Tarnopolsky, M. A. The potential of endurance exercise-derived exosomes to treat metabolic diseases. Nature Reviews Endocrinology 12, 504–517 (2016).
6 Mol, E.A., Goumans, M.J., Sluijter, J.P.G. Cardiac Progenitor-Cell Derived Exosomes as Cell-Free Therapeutic for Cardiac Repair. Advances in Experimental Medicine and Biology 998, 207-219 (2017)
7 Kim, M. S., et al. Development of exosome-encapsulated paclitaxel to overcome MDR in cancer cells. Nanomedicine: Nanotechnology, Biology, and Medicine 12 655–664 (2016)