Dr. Chris Centeno
Regenexx Blog
3-19-18

https://www.regenexx.com/what-are-ex...-do-they-work/

What are Exosomes? Are They Better than Stem Cells?
You may have recently seen physicians advertising exosome therapy. Or if you’re a doctor, you may have been hit up by a sales rep claiming to sell exosomes. What the heck are exosomes? Are they better than stem cells? How do they work? Let’s delve into this topic this morning

What Are Exosomes?
Cells communicate with each other using cytokines. These are proteins that are excreted by one cell and tell another cell what to do. This is one of the ways stem cells work, by orchestrating a repair response through other cells, like a conductor making sure all of the instruments produce beautiful music instead of noise.

Exosomes are little packets of stuff that bud off the outer wall of the cell. They contain everything from proteins to RNA. However, the really cool thing they can carry is mRNA.

What Is mRNA?
mRNA makes proteins. Think of it as the instruction set for certain proteins and the factory that makes them. These proteins can include everything from building blocks to chemical signals.

Cell Culture and Exosomes
When stem cells are being cultured or growing, you find exosomes in the growth media. Harvesting these and injecting them into patients has been proposed as treatment as they can contain both cytokines and mRNA capable of stimulating repair. However, there’s a bit more complexity to this story.

Exosomes Are Like Missiles
An exosome is like a missile fired by a stem cell toward a target cell. It has a payload, which is either a protein that can tell a cell what to do or mRNA, which can force the other cell to make proteins that the stem cell needs.

Dumb Missiles vs. Smart Bombs
The fantastic thing about stem cells is that they detect their environment and then act accordingly. Repairing tissue is a complex dance of cells receiving the right chemical stimulus at exactly the right time. The exosomes collected from the media of stem cells in culture are those that are needed to grow cells in culture. Basically, the signals or cross talk between cells. Given that stem cell culture is not a repair environment, the payloads of these exosomes have little to do with the repair of a complex injury. Hence, these exosomes are like missiles with the wrong, or at least not an optimal, payload. They are “dumb missiles” if collected and used as a therapy.

When stem cells are in their own environment and detect tissue that needs repair, they release exosomes that are loaded with payloads for the proteins and mRNA involved in tissue repair. They also shoot these “smart bombs” at the specific cells in the local area that are involved in the construction job and release exosomes with different payloads at different times. All of these signals are what the local environment needs to help repair the damage.

The Regulatory Issues with Exosomes
Right now, culturing stem cells in the U.S. is not permitted. Since the most common way to obtain exosomes is culturing stem cells, exosomes obtained this way are an unapproved drug product. In addition, if a company tries to isolate exosomes from something like amniotic fluid and makes claims that these can repair tissue, this is also an unapproved drug.

The upshot? Exosomes are pretty cool, but using them as therapy isn’t quite yet fully baked. Why? This is because this is a “dumb” therapy. Meaning that the nice thing about stem cells is that they’re smart and detect what’s needed to repair tissue. Hence, stem cells use exosomes like missiles, firing them at the local cells at the exact right time and in the right sequence. Knowing which payloads to load on those missiles, when, and why is something that a stem cell knows how to do and we don’t yet fully understand.