Is PRP is an Exosome Treatment?

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exosome treatment

I’ve become pretty used to the fads in regen med that I’ve witnessed for the last decade and a half. It seems like every year or two something gets hot and then eventually fizzles out and then it’s on to the next thing. Right now that hot item is exosome treatment. The funny thing is that if you’ve already used or had PRP, you have already experienced an exosome therapy. Let me explain.

Exosomes as Penicillin?

I’ve had physicians tell me that exosome treatment is the Penicillin of the 21st century. Most only understand what an exosome is at a basic level. For example, they generally know that an exosome is produced by a cell and that it can affect other cells (1). They kind of know that exosomes can carry different types of things like mRNA and growth factors (2), but that’s where their understanding stops. However, let’s learn more.

There are Hundreds of Different Types of Exosomes

If we stick with the Penicillin analogy, we know that this is an antibiotic. We also know that antibiotics are a type of drug and that there are thousands of different drugs which all have different effects on the body. Some can help certain diseases and some do nothing for other diseases. Exosomes are just the same. There are at least several hundred different types that can all do different things and these can be identified via flow cytometry (16). The problem right now is that nobody is clear on how to isolate specific exosomes that do specific things like repairing your cartilage or nerves.

In addition, not all exosomes are good. For example, in one study, two were identified that were associated with a higher mortality rate in ICU patients (10). In addition, there’s an evolving area of research that rare and deadly prions hitch a ride in exosomes (24).

PRP is an Exosome Treatment

The exosome treatment sales crowd is heavily focused on creating products mostly derived from birth tissues. However, what they forget is that just about every cell in your body produces exosomes and this even extends to non-cellular fragments like platelets. So is platelet-rich plasma (PRP) an exosome therapy?

We all know that platelets clot the blood and then release their growth factor contents via vesicles to promote local healing. However, as shown above, they also release exosomes just like cells. These begin as multivesicular bodies (MVBs) inside the platelet.

Platelets release hundreds of different types of exosomes (9,11,13,14,19, 21). In addition, these exosomes will survive bursting the platelet open to create platelet lysate, which in part works through exosomes (23). As with cells, what’s in the exosomes that are released depends on what the platelet senses in its local environment and when (25). For example, it was found that using a platelet-derived exosome treatment to heal wounds needs to be carefully timed to maximize results (6). This is obviously something normally handled by the platelet which detects what needs to be delivered and then releases that growth factor or exosome at the specific moment when it’s needed.

Exosomes released by platelets play a big role in blood vessel and cardiac disease protection and repair (3, 4,8,11,15) As a result, it makes sense that platelets release exosomes after exercise (7). Basically, acting to maintain and right-size the vasculature needed to support more physical activity.

Platelet-derived exosomes are also known to have key therapeutic effects. For example, platelet exosomes can cross the Blood-Brain Barrier and participate in new neuron growth (5). An exosome treatment derived from PRP can also heal diabetic skin wounds and even prevent cell death in osteonecrosis (a bone death disease) (17, 20).

In addition, the science behind platelets and exosomes is so robust that we even know what impacts their release. For example, the drug used to activate platelets determines the types of exosomes released (18). Also, different drugs taken by the patient can also change the payloads in the exosomes. For instance, aspirin reduced the total number of proteins in platelet released exosomes (22).

The upshot? PRP is an exosome treatment. The big difference is that platelets are intelligent machines that know which types of exosomes to release and when. You don’t get that when you just dump a bunch of isolated exosomes into an area and hope for the best.

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References:

(1) Yin K, Wang S, Zhao RC. Exosomes from mesenchymal stem/stromal cells: a new therapeutic paradigm. Biomark Res. 2019;7:8. Published 2019 Apr 4. doi: 10.1186/s40364-019-0159-x

(2) Kusuma GD, Carthew J, Lim R, Frith JE. Effect of the Microenvironment on Mesenchymal Stem Cell Paracrine Signaling: Opportunities to Engineer the Therapeutic Effect. Stem Cells Dev. 2017 May 1;26(9):617-631. doi: 10.1089/scd.2016.0349.

(3) Yao Y, Sun W, Sun Q, et al. Platelet-Derived Exosomal MicroRNA-25-3p Inhibits Coronary Vascular Endothelial Cell Inflammation Through Adam10 via the NF-κB Signaling Pathway in ApoE-/- Mice. Front Immunol. 2019;10:2205. Published 2019 Oct 2. doi: 10.3389/fimmu.2019.02205

(4) Zhang W, Dong X, Wang T, Kong Y. Exosomes derived from platelet-rich plasma mediate hyperglycemia-induced retinal endothelial injury via targeting the TLR4 signaling pathway. Exp Eye Res. 2019 Dec;189:107813. doi: 10.1016/j.exer.2019.107813.

(5) Leiter O, Walker TL. Platelets: The missing link between the blood and brain? Prog Neurobiol. 2019 Dec;183:101695. doi: 10.1016/j.pneurobio.2019.101695.

(6) Henriques-Antunes H1, Cardoso RMS, Zonari A, et. al. The Kinetics of Small Extracellular Vesicle Delivery Impacts Skin Tissue Regeneration. ACS Nano. 2019 Aug 27;13(8):8694-8707. doi: 10.1021/acsnano.9b00376.

(7) Brahmer A, Neuberger E, Esch-Heisser L, et al. Platelets, endothelial cells and leukocytes contribute to the exercise-triggered release of extracellular vesicles into the circulation. J Extracell Vesicles. 2019;8(1):1615820. Published 2019 May 28. doi: 10.1080/20013078.2019.1615820

(8) Kuravi SJ, Harrison P, Rainger GE, Nash GB. Ability of Platelet-Derived Extracellular Vesicles to Promote Neutrophil-Endothelial Cell Interactions. Inflammation. 2019;42(1):290–305. doi: 10.1007/s10753-018-0893-5

(9) Parsons MEM1, Szklanna PB1, Guerrero JA, et. al. Platelet Releasate Proteome Profiling Reveals a Core Set of Proteins with Low Variance between Healthy Adults. Proteomics. 2018 Aug;18(15):e1800219. doi: 10.1002/pmic.201800219.

(10) Danesh A, Inglis HC, Abdel-Mohsen M, et al. Granulocyte-Derived Extracellular Vesicles Activate Monocytes and Are Associated With Mortality in Intensive Care Unit Patients. Front Immunol. 2018;9:956. Published 2018 May 8. doi: 10.3389/fimmu.2018.00956

(11) Walsh TG, Poole AW. Do platelets promote cardiac recovery after myocardial infarction: roles beyond occlusive ischemic damage. Am J Physiol Heart Circ Physiol. 2018;314(5):H1043–H1048. doi: 10.1152/ajpheart.00134.2018

(12) De Paoli SH, Tegegn TZ, Elhelu OK, Strader MB, et al. Dissecting the biochemical architecture and morphological release pathways of the human platelet extracellular vesiculome. Cell Mol Life Sci. 2018 Oct;75(20):3781-3801. doi: 10.1007/s00018-018-2771-6.

(13) Preußer C, Hung LH, Schneider T, et al. Selective release of circRNAs in platelet-derived extracellular vesicles. J Extracell Vesicles. 2018;7(1):1424473. Published 2018 Jan 15. doi: 10.1080/20013078.2018.1424473

(14) Tao SC, Guo SC, Zhang CQ. Platelet-derived Extracellular Vesicles: An Emerging Therapeutic Approach. Int J Biol Sci. 2017;13(7):828–834. Published 2017 Jul 6. doi: 10.7150/ijbs.19776

(15) Li J, Tan M, Xiang Q, Zhou Z, Yan H. Thrombin-activated platelet-derived exosomes regulate endothelial cell expression of ICAM-1 via microRNA-223 during the thrombosis-inflammation response. Thromb Res. 2017 Jun;154:96-105. doi: 10.1016/j.thromres.2017.04.016.

(16) Nolan JP, Jones JC. Detection of platelet vesicles by flow cytometry. Platelets. 2017;28(3):256–262. doi: 10.1080/09537104.2017.1280602

(17) Tao SC, Yuan T, Rui BY, Zhu ZZ, Guo SC, Zhang CQ. Exosomes derived from human platelet-rich plasma prevent apoptosis induced by glucocorticoid-associated endoplasmic reticulum stress in rat osteonecrosis of the femoral head via the Akt/Bad/Bcl-2 signal pathway. Theranostics. 2017;7(3):733–750. Published 2017 Jan 15. doi: 10.7150/thno.17450

(18) Yang Y, Zhang W, Cheng B. Experimental research on the effects of different activators on the formation of platelet-rich gel and the release of bioactive substances in human platelet-rich plasma. Zhonghua Shao Shang Za Zhi. 2017 Jan 20;33(1):12-17. doi: 10.3760/cma.j.issn.1009-2587.2017.01.004.

(19) Brisson AR, Tan S, Linares R, Gounou C, Arraud N. Extracellular vesicles from activated platelets: a semiquantitative cryo-electron microscopy and immuno-gold labeling study. Platelets. 2017 May;28(3):263-271. doi: 10.1080/09537104.2016.1268255

(20) Guo SC, Tao SC, Yin WJ, Qi X, Yuan T, Zhang CQ. Exosomes derived from platelet-rich plasma promote the re-epithelization of chronic cutaneous wounds via activation of YAP in a diabetic rat model. Theranostics. 2017;7(1):81–96. Published 2017 Jan 1. doi: 10.7150/thno.16803

(21) Aatonen M, Valkonen S1, Böing A, Yuana Y, Nieuwland R, Siljander P. Isolation of Platelet-Derived Extracellular Vesicles. Methods Mol Biol. 2017;1545:177-188. https://www.ncbi.nlm.nih.gov/pubmed/27943214

(22) Goetzl EJ, Goetzl L, Karliner JS, Tang N, Pulliam L. Human plasma platelet-derived exosomes: effects of aspirin. FASEB J. 2016;30(5):2058–2063. doi: 10.1096/fj.201500150R

(23) Torreggiani E, Perut F, Roncuzzi L, Zini N, Baglìo SR, Baldini N. Exosomes: novel effectors of human platelet lysate activity. Eur Cell Mater. 2014 Sep 22;28:137-51; discussion 151. https://www.ncbi.nlm.nih.gov/pubmed/25241964

(24) Saá P, Yakovleva O, de Castro J, et al. First demonstration of transmissible spongiform encephalopathy-associated prion protein (PrPTSE) in extracellular vesicles from plasma of mice infected with mouse-adapted variant Creutzfeldt-Jakob disease by in vitro amplification. J Biol Chem. 2014;289(42):29247–29260. doi: 10.1074/jbc.M114.589564

(25) Aatonen MT, Ohman T, Nyman TA, Laitinen S, Grönholm M, Siljander PR. Isolation and characterization of platelet-derived extracellular vesicles. J Extracell Vesicles. 2014;3:10.3402/jev.v3.24692. Published 2014 Aug 6. doi: 10.3402/jev.v3.24692

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Chris Centeno, MD

Regenexx Founder

Chris Centeno, MD is a specialist in regenerative medicine and the new field of Interventional Orthopedics. Centeno pioneered orthopedic stem cell procedures in 2005 and is responsible for a large amount of the published research on stem cell use for orthopedic applications.
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