Exosome Therapy vs Stem Cell Therapy

exosomes therapy vs stem cell therapy

Exosomes as the Next Big Thing

Lately the world has been looking towards the next big thing in the field of medicine. The field of medicine is quickly becoming layered, and new technologies are constantly being introduced. One of these technologies is exosome therapy. So, what is exosome therapy? Basically, exosomes are tiny micron-sized packages that cells secrete which contain all the materials needed to build different parts of the cells. Exosomes also carry on their surface some genes, cytokines and other molecules which help the stem cells to find, maintain and repair tissue. Exosomes can be administered through injection or through inhalation.

Stem cell safety and efficacy shortcomings

The first key issue with stem cell therapy is the question mark over safety. Introducing foreign living cells into a system as complex as the human body is challenging.

Predicting the cell’s behaviour once injected is a problem, FDA experts say.

A growing list of cautionary examples catalogue how things can go wrong when unproven stem cell therapies are used in the clinic; from a kidney failure patient who developed tumours following stem cell therapy, to patients with an age-related eye condition called macular degeneration, who were left blinded by their therapy given at a US clinic3.

In late 2018 and after infections linked to unapproved stem cell treatments sent 12 people to hospital, the FDA issued a stern warning about the cell products4.

Some ‘autologous’ therapies using the patient’s own cells have also become notorious in certain countries and the subject of doubtful or dangerous medical tourism.

Today, the only stem cell therapy that has received FDA approval in the regenerative medicine field is the use of blood-forming stem cells for patients with specific blood production disorders.

Stem cells appear to be making little progress toward FDA-approved clinical use. Little wonder, then, that regenerative medicine researchers are increasingly turning to exosomes: packets of beneficial biomolecules released by stem cells.

Exosomes – regenerative medicine 2.0

We now know that the old working hypothesis for how stem cells exert their regenerative effects was wrong. The transplanted stem cells don’t stick around long in the recipient’s body to replace damaged cells; most are cleared within a week.

As researchers from Oxford5 to Scripps6 have now concluded, it’s the exosomes stem cells release, rather than the cells themselves, that impart the regenerative benefit.

Exosomes are being described as the ‘secret sauce’ of stem cells. Exosome therapy would avoid all the problems of a therapy based on live stem cells and yet harness a natural regenerative capability from stem cells.

Tellingly, some biotech stocks established back in the early 2000s as stem cell companies have shifted their focus to exosome research.

Exosomes could be harvested from stem cells housed in a bioreactor and then purified as a proper drug product to be administered by injection or infusion.

Exosomes should be a simpler, safer, lower cost, more easily stored and transported, alternative to stem cells.

Critically, exosomes are inherently less risky that live stem cell transplants. Exosomes cannot replicate; they cannot transform into malignant cells or other harmful cell types; they are less likely to trigger an immunogenic response; they cannot be infected with virus.

As a further demonstration of their safety, blood plasma contains high concentrations of unmatched exosomes, and blood transfusions have been carried out in hospitals for decades.

And exosomes should have an efficacy advantage, too. Being much smaller than whole cells, exosomes can circulate much more easily through the body to reach sites of injury or disease and trigger healing.

Early academic clinical studies are starting to prove exosomes’ potential. A recent placebo-controlled trial on 40 patients with advanced chronic kidney disease showed that the patients receiving exosomes saw enhanced kidney function at 12 months after treatment and no adverse events in the treatment group7.

Exosomes to drive regeneration

Exosomes administered to patients could exert their regenerative effects in a number of ways – giving treatment by exosomes multiple shots at goal.

Some degeneration, such as Parkinson’s Disease, is due to a loss of specialized cells over time. Struggling cells that take up exosomes can be rescued from programmed cell death (apoptosis), and restored to health, thanks to the regenerative genetic material and the protein and lipid cellular building blocks that the exosome delivers.

Degeneration with age has also been associated with an increase in senescence cells. Senescent cells are like ‘zombie cells’ that don’t undergo normal clearance, yet cannot divide and proliferate to generate new tissue.

Recent research points to a benefit in animal models of human disease when the number of senescent cells is reduced. In 2019 researchers published that exosomes and vesicles from stem cells can alleviate cellular aging (senescence) in cells exposed to the exosomes/vesicles8.

Exosomes can also play a role in a recently discovered, previously unsuspected regenerative process in our bodies. Exosomes can trigger fully differentiated, specialized cells such as liver cells (‘hepatocytes’) to a ‘de-differentiate’ into a more stem cell-like state cell type9 and then maintain a pool of progenitor cells that can replenish the damaged liver with new cells10.

This same mechanism could be used to treat cardiac disease (e.g. cardiac ischemia where a lack of blood flow leads to cardiac muscle cell death). Normally a damaged heart fails to regenerate and becomes fibrotic with scar tissue.

Unfortunately, the scar tissue doesn’t have the capacity to beat like cardiomyocytes, so increased fibrosis leads to progressive loss of heart pumping ejected volume and impairment or death. But using exosomes to reprogram the patient’s own heart muscle cells into cardiac progenitor stem cells offers a new way to treat cardiac damage and drive regeneration.

Clearing the hurdles for exosomes as drugs

Exosome therapy vs stem cell therapy: Exosomes could be a better medicine than live stem cells – a way to harness stem cells’ regenerative power without all the problems and disappointment.

But while stem cells secrete trillions of exosomes naturally, efficient separation and purification of exosomes has proven to be very difficult indeed11. Until now.

1 Marks, P.W., Witten, C.M., & Califf, R. M. Clarifying Stem-Cell Therapy’s Benefits and Risks. New England Journal of Medicine 376, 1007 (2017)2 Cuende, B., et al Cell, tissue and gene products with marketing authorization in 2018. Worldwide Cytotherapy, 2018; 20: 1401-14133 Kuriyan, A. E., et al. Vision Loss after Intravitreal Injection of Autologous “Stem Cells” for AMD. New England Journal of Medicine 376, 1047 (2017)4 Andaloussi, S. E. L., Mäger, I., Breakefield, X. O., & Wood, M. J. A. Extracellular vesicles: biology and emerging therapeutic opportunitiesNature Reviews Drug Discovery 12, 347 (2013)6 Phinney, D. G. & Pittenger, M. F. Concise Review: MSC-Derived Exosomes for Cell-Free Therapy. Stem Cells 35, 851 (2017)7 Nassar, W., et al. Umbilical cord mesenchymal stem cells derived extracellular vesicles can safely ameliorate the progression of chronic kidney diseasesBiomaterials Research 20, 21 (2016)8 Liu, S., et al Highly purified human extracellular vesicles produced by stem cells alleviate aging cellular phenotypes of senescent human cells. Stem Cells 37, 779 (2019)9 Lee, HH., et al. Exosomes from mesenchymal stem cells induce the conversion of hepatocytes into progenitor oval cells. Stem Cell Res Ther. 23;8(1):117 (2017)10 Mistry, D., Progenitor Function in Self-Renewing Human Epidermis is Maintained by the Exosome. Cell Stem Cell 11(1): 127–135 (2012)11 Colao, I. L., et al. Manufacturing Exosomes: A Promising Therapeutic Platform. Trends in Molecular Medicine 24, 242 (2018)