The exosomes released by stem cells look a far more promising therapy than cells themselves for tackling age-related diseases.

Despite a decade and a half of research, the safety and efficacy of stem cell therapy has still not been proven, experts from the US Food and Drug Administration (FDA) recently concluded in the New England Journal of Medicine.1

Stem cell therapy once seemed beguilingly simple. These regenerative cells naturally migrate to sites of damage or disease in the body. Once there, it was thought, the cells nestle into these sites of injury, and directly replace damaged cells.

By injecting additional stem cells into the body, this regenerative process could be enhanced. Animal studies and early human trials appeared to bear the idea out.

But it soon turned out that a therapy based on transplanting living cells into the body was anything but simple. Introducing living cells into a system as complex as the human body makes it challenging, if not impossible, to predict the cell’s behaviour once injected, 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 clinic.2

Stem cells appear to 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 (see Exosomes 101).

As we now know, 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 Oxford3 to Scripps4 have now concluded, it’s the exosomes stem cells release, rather than the cells themselves, that imparts the regenerative benefit.

Stem cell therapy, simplified

Exosome therapy would avoid all the problems of a therapy based on live stem cells as they are not living cells. More akin to a conventional biologic drug, exosomes should be a simpler, lower cost, easy to store and transport, alternative to stem cells.

Critically, exosomes are inherently less risky than 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 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 clinical studies are starting to prove exosomes’ potential. In 2016, a placebo-controlled trial on 40 patients with advanced chronic kidney disease showed that the patients receiving exosomes saw enhanced kidney function. Patients were tracked for twelve months and no safety concerns were reported.5

So what’s holding exosome research back? The bottleneck has been the laborious and inefficient techniques to isolate and purify exosomes from stem cells.6 With their proprietary LEAP process for purifying a well-defined set of exosomes efficiently and in high yield, Exopharm has the technology to take exosome therapy into the clinic.


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 – Kuriyan, A. E., et al. Vision Loss after Intravitreal Injection of Autologous “Stem Cells” for AMD. New England Journal of Medicine 376, 1047 (2017)

3 – Andaloussi, S. E. L., Mäger, I., Breakefield, X. O., & Wood, M. J. A. Extracellular vesicles: biology and emerging therapeutic opportunities. Nature Reviews Drug Discovery 12, 347 (2013)

4 – Phinney, D. G. & Pittenger, M. F. Concise Review: MSC-Derived Exosomes for Cell-Free Therapy. Stem Cells 35, 851 (2017)

5 – Nassar, W., et al. Umbilical cord mesenchymal stem cells derived extracellular vesicles can safely ameliorate the progression of chronic kidney diseases. Biomaterials Research 20, 21(2016)

6 – Lerner, T., et al. Applying Extracellular vesicles based therapeutics in clinical trials – an ISEV position paper. Journal of Extracellular Vesicles 4, 30087 (2015)