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Exosome therapy has exploded in the past few years. So what is this? How do exosomes work? Are exosomes stem cells? How much do we know about whether exosomes are effective?

What is Exosome Therapy? How Do Exosomes Work?

Exosomes are small packets of information excreted by all living cells (1). They are literally how cells communicate with one another. They can contain everything from growth factors and/or cytokines to instructions to reprogram other cells.

To get a sense of what they are, watch my video below:

The basic idea behind exosome therapy is that by using these messages that stem cells send to other cells, you can get rid of the need for using the cells (2). However, as discussed in the video, since stem cells sense their environment and then send out specific repair messages to other cells based on what they detect, just using the exosomes without also tuning that message could be a big problem (3).

Are Exosomes Stem Cells?

Stem cells are cells that can repair tissue (6). They do this either by turning into a needed damaged cell type (differentiation) or by excreting chemicals or exosomes as instructions to other cells on how to repair tissue (paracrine signaling). Exosomes are the instructions issued by the stem cell, so they are not a stem cell.

How Much Do We Know About the Efficacy of Exosome Therapy?

While the idea of exosome therapy has great promise, there are lots of things to be dialed in yet:

1. What type of exosomes help to repair what kind of tissue? There are many different types.
2. Does exosome therapy actually work when tested in real patients with real problems?

To help you understand how much we don’t yet know about exosome therapy, I’ve chosen a common problem that’s being treated with exosomes-knee arthritis. In the infographic above I’ve listed every high-level study in real patients that we have for PRP, all studies on Bone Marrow Stem Cells, and what we have on Exosomes.

First up is platelet-rich plasma (PRP). This is where the doctor takes blood from a vein and spins out the platelets in a centrifuge, concentrating them in plasma. The platelets excrete healing growth factors, hence PRP is used to help heal many chronic injuries including to help knee arthritis (7). In addition, platelets excrete exosomes just like stem cells (4,5). There are 27 randomized controlled trials on the use of PRP for knee arthritis (each is a circle above).

Next up are bone marrow stem cells. These are mesenchymal stem cells derived from a patient’s own or someone else’s bone marrow (8). As reviewed, they can detect what’s needed in the local environment and then excrete specific chemicals or exosomes to help repair tissue. As of a few months ago, there were 58 studies (each is a circle above) reporting the experience of thousands of patients who all used bone marrow stem cells to treat their knee arthritis.

Finally, we have exosomes used to treat knee arthritis. If you look above, you see only a dashed circle with nothing in it under the category of exosomes. Why? As of this writing, we don’t have a single study that has tested the use of exosome therapy to treat knee arthritis in real patients. So right now, given the extensive research on PRP and bone marrow stem cells, both of which excrete exosomes, why would you get rid of the platelets and stem cells and just inject exosomes into someone’s knee?

There are No Exosome Studies for Any Clinical Condition

It really doesn’t matter if you have knee arthritis a bum shoulder, a bad ankle, erectile dysfunction, a neurological problem, or just are trying to combat aging, we have zero clinical research that exosomes will do anything for your condition. This doesn’t mean that you won’t find doctors pushing exosomes or even listing basic science research on animals on their websites. However, now you know the actual truth, we have no idea whether exosomes will help your problem.

The upshot? while exosome therapy shows great promise, please don’t be fooled. You’re much better off sticking with other regenerative medicine options that actually have published research showing what happens when patients are treated then taking a chance with exosomes.

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References:

(1) Vakhshiteh F, Atyabi F, Ostad SN. Mesenchymal stem cell exosomes: a two-edged sword in cancer therapy. Int J Nanomedicine. 2019;14:2847–2859. Published 2019 Apr 23. doi: 10.2147/IJN.S200036

(2) 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

(3) 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.

(4) 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

(5) 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.

(6) Berebichez-Fridman R, Montero-Olvera PR. Sources and Clinical Applications of Mesenchymal Stem Cells: State-of-the-art review. Sultan Qaboos Univ Med J. 2018;18(3):e264–e277. doi: 10.18295/squmj.2018.18.03.002

(7) Alves R, Grimalt R: A Review of Platelet-Rich Plasma: History, Biology, Mechanism of Action, and Classification. Skin Appendage Disord 2018;4:18-24. doi: 10.1159/000477353

(8) Charbord P. Bone marrow mesenchymal stem cells: historical overview and concepts. Hum Gene Ther. 2010;21(9):1045–1056. doi: 10.1089/hum.2010.115

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. View Profile