Could exosome therapy help athletes recover from injury faster – and help the rest of us by mimicking the whole-body benefits of exercise?

Some people don’t get enough physical exercise – but others suffer from too much activity, injury and overtraining. Many sports players are set to benefit from the dawning era of exosome medicine. The regenerative effects of exosome injections may help speed the recovery of many sports-related injuries – as well as injuries picked up at work or around the home – a plethora of publications are beginning to show. Sports injuries come in many forms, from muscle tears to tendon (connective tissue) and cartilage (joint) damage. Sometimes the injury is immediately obvious – the snapped tendon is a good example. But in the case of cartilage and joint overload, it can take decades for the injury to make itself felt – usually in the form of osteoarthritis, a painful swelling and stiffening of the joints. Worldwide, 250 million people are affected by this chronic condition.

Currently there is no cure for osteoarthritis, only treatments to ease the symptoms. Sealed away within the joint and with little blood supply, the damaged cartilage cells have little capacity for self-repair. Injections of specialised cells (chondrocytes) or mesenchymal stem cells (MSCs) into the joint may slow down the disease progression or even promote cartilage regeneration [1, 2]. But the benefit of these therapies is still unproven and their use comes with all the costs and complications of treating patients with live cells (see Exosomes versus Stem Cells).
Osteoarthritis researchers have already turned their attention to the benefits of regenerative exosomes to treat osteoarthritis [3]. It is now widely accepted that it is not the stem cells themselves, but the nanoscopic packets of signalling molecules they release – exosomes – that are the therapeutically active aspect of stem cell therapy. A successful animal study of cartilage regeneration following exosome therapy has paved the way for human clinical trials [4]. MSC-derived exosomes are equally promising therapy for accelerating the healing of tendon injury [5] or bone fractures [6]. Even muscle injuries could benefit from extra exosomes. So treatment with exosomes could help our top sports people perform better and help all of us recover from over-exertion faster.

Exosomes are already at the scene
Another product used to treat injury is a blood extract known as platelet rich plasma (PRP), usually made from spinning-down the patient’s own blood and removing the red blood cells. Although evidence for PRP therapy is contentious, trials over the last few years have tested the idea that PRP could speed the healing of muscle, tendon and other soft tissue injuries. Although some trials have found no effect, other studies have shown PRP can significantly cut healing time – leading some researchers to suggest that the timing of PRP injection after injury is critical [7]. The theory behind the PRP therapy is that a localised injection of PRP is a rich concentration of regenerative components such as growth factors, cytokines and thrombocytes (blood clotting cells) – which together accelerate healing at the injection site. Recent research has shown that PRP is also rich in exosomes and that exosomes isolated from PRP can themselves (and alone) deliver the therapeutic benefit of PRP [8, 9].

Exercise in a bottle instead of a gym?
Hop onto a treadmill or exercise bike at the gym, and there’s an almost immediate flood of exosomes released into the bloodstream as your legs start working on the machine. This rush of these packets of signalling molecules into the bloodstream could be behind the body-wide benefits of exercise, new research suggests [10]. Humans have evolved to be good at endurance and benefit from exercise. Endurance exercise has well-documented benefits to the body – and even the brain, delaying the progression of cognitive impairment in the elderly [11]. Mark Tarnopolsky from McMaster University in Canada and his colleagues argue that exosomes released during exercise probably play a key role in the system-wide benefits of going running or working out at the gym [12]. What’s more, they suggest that exercise-derived exosomes – taken from fit and healthy young athletes, or bioengineered in the lab – could offer a new way to treat obesity and its related diseases in patients unable to get the direct benefits of exercise. Exosomes could be ‘nature’s exercise pill’, they suggest [12].
According to the World Health Organization, around 3.2 million deaths around the globe per year can be attributed to insufficient exercise – if exosomes can mimic exercise then it is a big deal for many of us who avoid the gym.

Who you gonna call? Call exosomes!
There is something invisible in your neighbourhood, it is good and it is exosomes.
Exosomes are a natural but invisible (except under an electron microscope) part of our lives.
Researchers are now uncovering ways that we can harness exosomes to help us heal and to allow us mimic the benefits of exercise without the downsides.

Exosomes will be here soon to help you.

Exopharm (www.exopharm.com) is a leader in bringing exosomes into medical practice.

References[1] Mobasheri, A., et al., Chondrocyte and mesenchymal stem cell-based therapies for cartilage repair in osteoarthritis and related orthopaedic conditions. Maturitas 78, 188-98 (2014).[2] Kim, Y.S., Choi, Y.J., Koh, Y.G. Mesenchymal Stem Cell Implantation in Knee Osteoarthritis. The American Journal of Sports Medicine 43, 2293-2301 (2015).[3] Toh, W. S., Laid, R. C., Hui, J. H. P. & Lim, S. K. MSC exosome as a cell-free MSC therapy for cartilage regeneration: Implications for osteoarthritis treatment. Seminars in Cell & Developmental Biology 67, 56-65 (2017).[4] Zhang, S., Chu, W.C., Lai, R.C., Lim, S.K., Hui, J.H.P. & Toh, W.S. Exosomes derived from human embryonic mesenchymal stem cells promote osteochondral regeneration. Osteoarthritis and Cartilage 24, 2135–2140 (2016).[5] Tetta, C. et al. The role of microvesicles derived from mesenchymal stem cells in tissue regeneration; a dream for tendon repair? Muscles, Ligaments and Tendons Journal 2, 212-221 (2012).[6] Burke, J., Kolhe, R., Hunter, M., Isales, C., Hamrick, M. & Fulzele, S. Stem Cell-Derived Exosomes: A Potential Alternative Therapeutic Agent in Orthopaedics. Stem Cells International 2016, 5802529 (2016).[7] Anitua, E., Sánchez, M. & Padilla, S. More on Platelet-Rich Plasma Injections in Acute Muscle Injury. New England Journal of Medicine 371, 1264-1265 (2014).[8] Torreggiani, E., Perut, F., Roncuzzi, L., Zini, N., Baglìo, S.R., Baldini, N. Exosomes: Novel Effectors Of Human Platelet Lysate Activity. European Cells and Materials 28, 137-151 (2014).[9] Guo, S.-C., Tao, S.-C., Yin, W.-J., Qi, X., Yuan, T., and Zhang, C.-Q. Exosomes derived from platelet-rich plasma promote the re-epithelization of chronic cutaneous wounds via activation of YAP in a diabetic rat model. Theranostics 7, 81–96 (2017).[10] Fruhbeis, C., Helmig, S., Tug, S., Simon, P. & Kramer-Albers, E. M. Physical exercise induces rapid release of small extracellular vesicles into the circulation. Journal of Extracellular Vesicles 4, 28239 (2015).[11] Carvalho, A. et al. Physical activity and cognitive function in individuals over 60 years of age: a systematic review. Clinical Interventions in Aging 9, 661-82 (2014).[12] 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).