√ As Exosome Work Advances, Clinics Pitch Unproven Therapies To Patients

Electron microscopy image of exosomes, image labeled for reuse on the web.

Time to sell exosome therapies to patients? No.

Some stem cell clinics and related firms are looking for new ways to make profits and toward that goal a few have latched onto the legitimate buzz around exosome research.

What are exosomes?

Imagine if you could bubble up a pea-sized sphere off your skin full of good stuff without harming yourself and toss it over to your relative or friend like a mini-water balloon toss, whose skin would fuse with it and absorb the goodies in side, then becoming healthier.

Sounds like sci-fi at that imagined human scale, but cells do this kind of thing quite often. The cellular ‘water balloons’ are exosomes, tiny subcellular packages containing unique mixtures of various molecules including anything from RNA to proteins (check out this database of exosome contents, called ExoCarta).

Research shows that the cellular soup inside exosomes can influence cell behavior and there is a growing amount of legitimate work and excitement in this area. It’s not entirely clear that this cellular water balloon toss is always beneficial to other cells though.

A quick search on Clinicaltrials.gov found 95 study results, with the usual mix of relevant and not so relevant search results as well as more legit and less solid-looking listings, but overall this is a surprisingly large number of trials for this emerging area of biomedical research. You can see a map of trial locations below, with the U.S., Europe, and China leading the way.

Exosome clinical trials, map from Clinicaltrials.gov, August 23, 2018.

Just based on the state of the science, I believe that exosome research is not to the point where anyone should be directly marketing it to consumers (or indirectly to physicians) to try to make money, but people are doing this anyway lately and it seems centered on the supposed benefits of exosomes made specifically from stem cells.

One of the more recent examples of unproven stem cell exosomes apparently being sold comes from the story of a paralyzed former cheerleader and coach, Chico Garcia, looking for hope. Garcia is reportedly going to get “exosomes” from stem cells at a price tag of $11,000. The news story is short on details, but it mentions a physician:

“Dr. Douglas Spiel at the center said the way it works is they take very small products from young stem cells. Think of them as individual protein factories. They go to dormant cells in the body and inject the protein. The goal is for the proteins to help repair tissues in parts of the body that are not responding. “

A website for Stem Cell Center of NJ features Spiel and exosome therapies. For instance, there’s this passage.

“Dr. Spiel believes in ongoing self-education and study since the field of Regenerative Medicine is constantly evolving. He regularly attends, lectures and provides hands-on instruction for the Boston BioLife conferences multiple times per year. Besides having his own practice, Dr. Spiel is also Medical Director of Kimera Corporation, which is an international company providing Exosomes based out of Miami, Florida.”

On the NJ Center site it is claimed that exosomes might help various conditions including baldness, ED, spinal cord injury, neuropathy, and possibly stroke, although in the stroke section it is described (perhaps a typo) as “exome therapy” instead of “exosome therapy.” The exome is the collection of exon sequences in the genome. In my view the content on that page risks giving patients the wrong idea that exosomes are some kind of proven panacea.

“Kimera Corporation” mentioned in this quote is probably Kimera Stem Cell Labs/Kimera Labs, which seems to market some stem cells and exosomes. Dr. Spiel is listed on the Kimera site as its CMO.

There are others out there selling unproven exosome therapies as well and I expect the number is growing. I personally doubt the effectiveness of unproven stem cell exosomes as a therapy for many conditions.

Also, there will be risks. Sometimes exosomes from one cell that end up as part of another cell, may negatively influence the health of the other cell. Multiply that by billions or trillions and you can envision possible tissue damage in a hypothetical scenario of things gone wrong. My understanding is that exosome therapies are drugs, requiring an IND from the FDA and should go through clinical trials before being marketed to patients.

The bottom line is that in my view exosomes shouldn’t be sold to patients today even as I hope that in future years exosome therapies of some kind will be proven safe and effective from proper clinical trials.

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√ Dissecting 4 Possible Roles For Stem Cell Therapy Besides Cell Replacement

An illustration of stem cell drug delivery by Taylor Seamount Stem Cells: An Insider’s Guide by Paul Knoepfler.

Historically, the main route of proposed healing via stem cells was cell replacement. In this way of thinking the transplanted cells engrafted (took up home) in the patient’s tissue and replaced dead or diseased cells. However, interest continues to grow in other possible modes of healing by stem cells that don’t rely on cell replacement. In today’s post I cover 4 other possible mechanisms.

Secreted factors

An alternative, not mutually exclusive model to cell replacement is that stem cell transplants have beneficial effects via the factors they directly secrete. These growth factors, cytokines, and other molecules (collectively sometimes called “the secretome”) could have a positive impact by a number of mechanisms. After stem cell transplantation, these factors might tell endogenous stem or precursor cells to start growing. They could tell some cells not to die, while encouraging others that are beyond hope and might actually be mediating toxic effects to go ahead and croak. (Incidentally, you might have seen the research (mentioned here) supporting the notion that senescent cells hanging around the body are actually actively harmful and removing them could fight aging. There’s even a germinal field of “senolytics”.) Secreted molecules might also stimulate angiogenesis, aiding in tissue healing. It’s a fact of life that secreted factors produced by transplanted stem cells would also pose risks such as sparking cancer or enhancing the growth of an already existing, undetected tumor.

Immunosuppression

Another popular, related idea is that infused stem cell specifically have immunosuppressive functions. In this way of thinking, although injected stem cells don’t stay around a long time, while present they tell the immune system to “cool it”. It’s an interesting concept, but not concretely proven. Let’s say for the moment that it sometimes happens. In that context, we have to be very aware of risks associated with this hypothetical stem cell-mediated immunosuppression. For instance, patients may get sick from an infection or developing a tumor as a consequence of reduced immune activity. The immunosuppressive route of function has been discussed the most for mesenchymal stem cells or whatever you prefer the MSC acronym to stand for these days.

Exosomes

An additional idea invokes a different kind of “secretion” by cells. In addition to making molecules that are dumped out directly into the interstitial space, the blood, or onto neighboring cells, stem cells (and really all cells) make what are called exosomes. These are little, budded-off membrane-bound packages full of many different molecules. Exosomes can then deliver their soup of factors to other cells. There is a lot of legitimate excitement about exosomes and their possible clinical potential. Unfortunately, there is abundant hype too. Also, some unproven “exosome therapy” is already being sold to patients. Of course, if exosomes can have potential benefits, their function as little packages of potent molecules will also pose some risks, which at this point are not well understood.

Drug delivery

This last notion is related to the first three ideas above, but involves more time in the lab. Stem cells can be engineered in the lab to produce (or be loaded with) drugs that they then can secrete or in theory deliver with exosomes or even by cell fusion. In this way designer stem cells, once transplanted, can potentially deliver medicines to a diseased tissue. This delivery could even be on a cell-to-cell basis (I could say one cell acts as doctor and the other as patient, but I won’t), rather than systemically as most pharmaceutical drugs are given. For example, imagine stem cells loaded with chemotherapy delivering it directly to a brain tumor like a glioma.

Risks here include that the stem cells give too much drug, that the drug is delivered to the wrong cells, that the drug given by stem cells is uniquely toxic, or that the designer stem cells themselves engraft and grow into an undesired tissue or have some other negative effects. That last possibility is perhaps avoidable via a built in cellular su1cide switch.

You can see an illustration of envisioned stem cell-based drug delivery to a diseased region of brain in an illustration by Taylor Seamount for my book, Stem Cells: An Insider’s Guide, above.

Overall, what other possible, helpful non-cell replacement-based roles for transplanted stem cells come to mind?

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