Because of blogging here on The Niche and people giving me tips I often can see trends before they fully surface and a troubling new one is intranasal stem cell delivery by unproven clinics.
Over the past year I have heard of many clinics now offering this approach. I’ve seen this in marketing and heard from patients about it. There are potentially serious risks to this trend.
What is intranasal stem cell delivery?
Intranasal stem cell delivery is basically squirting or spraying mixtures of stem cells up a patient’s nose to try to get them into a region where there’s a health problem. This is a potentially promising delivery route for getting cells into the brain but requires careful study including with real clinical trials.
Why would a lot of clinics be switching to this approach?
One idea behind intranasal stem cell delivery by clinics is that it is a quick way to potentially get stem cells into the bloodstream. It’s also simpler than an IV infusion. I imagine that the simplicity is something that the clinics themselves appreciate as do many patients.
However, relatively few stem cells may actually get into the bloodstream this way compared to IV injection or infusion. This is a major potential downside.
In many cases patients may just sneeze out the cells or blow their noses leaving tissues full of stem cells for which they paid thousands of dollars. I wasn’t able to find good data demonstrating a robust delivery of stem cells through the nose into the bloodstream. Just because viral gene therapy or certain drugs can be administered through the nose doesn’t mean it’ll work for cells, which are much bigger.
Risks of intranasal stem cell delivery
Intranasal cell therapy delivery has not been well-studied and could have unique risks.
The major concern that comes to mind is accidental delivery of a large number of stem cells into the brain. Once there it’s hard to say what they might do. In that frontal brain location they are less likely to be quickly removed from the body as happens with IV injections.
Could cells squirted into the nose really get into the brain?
For years researchers have talked about the idea of an intranasal approach for direct cell therapy to the brain. The main alternatives are to literally drill a hole in the skull and inject cells into the brain with a fine needle or go into the spine. Notably, systemic IV infusions of cells does not seem to get many if any into the brain.
Data on nasal delivery of stem cells to the brain
In a recent PubMed search I found 27 articles focus on intranasal delivery of stem cells. Most of these studies were been done in rats or mice. They often reported that various kinds of stem cells can cross the nasal epithelium to get into the brain. Many are older articles.
A 2018 publication in Cell Transplantation gave more detail on the location of MSCs administered through the nose in rodents. They conclude:
Therefore, intranasally administered stem cells appear to cross the olfactory epithelium, enter a space adjacent to the periosteum of the turbinate bones, and then enter the SAS via its extensions adjacent to the fila olfactoria as they cross the cribriform plate. These observations should enhance understanding of the mode by which stem cells can reach the CNS from the nasal cavity and may guide future experiments on making intranasal delivery of stem cells efficient and reproducible.
It’s not clear to me how many cells in the subarachnoid space (SAS) might get into and impact the actual brain tissue itself in rodents or people.
A brand new paper in the journal Glia called Transnasal transplantation of human induced pluripotent stem cell-derived microglia to the brain of immunocompetent mice also reports getting cells into the brain through the nose. In this case they were human microglia made from IPS cells.
Overall, based on these reports there is a high likelihood that some clinics are accidentally getting stem cells into their customers’ brains. Some clinics may be intentionally trying to do this for neurological injury treatment. However, for others this risk may not be on their radar screen.
Clinical trial listings & clinics: MD Stem Cells, Ageless Regenerative Institute, R3 Stem Cell
A Clinicaltrials.gov search found 11 listings that mentioned intranasal stem cells. See map above.
The sponsor with the most listings was MD Stem Cells, which I see as a clinic-type firm that has been administering for-profit unproven stem cell treatments for years.
Another clinic firm, Ageless Regenerative Institute, was also listed as was the clinic firm R3 Stem Cell.
Out of the 11 listings, only a few seemed to possibly be like traditional clinical trials where you don’t have to pay.
Overall, while intranasal delivery of stem cells or other cells could have utility in some cases, without more data we just don’t know. I’m sure there are major risks to this approach too depending on many factors.
I really worry most about clinics possibly getting uncharacterized cells up inside their customers’ brains this way.
References
- The Route by Which Intranasally Delivered Stem Cells Enter the Central Nervous System, Cell Transplant, 2018.
- PubMed search for Intranasal stem cells in title words of papers, July 29, 2021.
- Clinicaltrials.gov search results, July 29, 2021.
Most of the clinics performing intranasal delivery for neurodegenerative problems use mannitol to shrink the olfactory mucosa so that relatively large stem cells (i.e., MSCs) can bypass the blood-brain barrier to gain access to the CNS. While mannitol can be used repeatedly for individuals younger than puberty, there is no harm and no foul. However, for individuals after puberty and adults, mannitol should be used only once. Two or more applications of mannitol to shrink the mucosa will form permanent channels between the olfactory epithelial cells. These permanent channels can then form permanent conduits for bacterial and viral access to the meninges, which can result in bacterial or viral meningitis.
What about intranasal administration of stem cells for nasal diseases?
That in theory might make sense but only if a clinical trial was done to test it for safety & whether it worked.
Interesting to see good ole “Ageless Regenerative Institute” listed.
That is an old co-creation of Kristin Comella of U.S. Stem Cell Inc (FDA/DOJ permanent injunction fame now) then known as “Bioheart” back in those days. Dr Sharon McQuillan is listed on the main LLC (now defunct) as filed in FL, but a simple Google search will show Kristin Comella as “Chief Science Officer” of that entity and many PR were issued claiming that “Bioheart has partnered with the Ageless Regenerative Institute” blah blah. It’s an old Kristin Comella gig gone defunct.
Dr McQuillan an actual MD, she filed suit against Comella and Bioheart in FL claiming they “stole” what she claims is what later became the “Comella method of how to make SVF from fat” protocol(s). McQuilan claims she paid Comella as a consultant to originally develop that supposed proprietary and unique “SVF protocol” (which never made sense to me – anyone can make SVF via numerous easy methods?) but McQuillan claimed the intellectual rights to, “How to make SVF from fat protocol” – again, easily found via a Google search.
I did not know they (McQuillan and Comella working together) were ever dinking around with intranasal fat derived SVF for “treating Alzheimer’s” which is what the clinicaltrials.gov site shows was their end goal.
https://www.magazine.medicaltourism.com/article/stem-cell-treatments-hope-hype-or-true-regenerative-medicine
Bottom of page shows the “article” was co-written by Dr Sharon McQuillan and Kristin Comella both listed as belonging to the “Ageless Regenerative Institute” in FL.
Mannitol increases osmotic pressure which the body neutralizes with water. If a clinic puts mannitol in IV solution the water content of blood should neutralize the mannitol before it ever reaches the brain. It is doubtful that mannitol in an IV would perform as those labs claim. Do they have any published papers to prove their claim?
My last comment was to Henry Young. I am not sure why it didn’t show up under his comment.
Some clinics administer mannitol IV before various types of IV stem cells. Their claim is that the mannitol opens the blood-brain barrier so the stem cells can enter the brain. What is your opinion on this and can this potentially cause similar problems you discussed above?
Dear Paul,
One of the problems usually not discussed with respect to intranasal delivery of stem cells for human application, but present in the Methods sections of the papers, is the use of mannitol to shrink the olfactory mucosa allowing large stem cells to gain entrance past the blood brain barrier. While that seems like a good method, there are inherent problems with that technique. In individuals with ages less than puberty, no harm no foul with respect to multiple applications of mannitol to the olfactory epithelium. However, for individuals older than puberty the use of mannitol on olfactory epithelium can occur only once with no harm no foul. However, two or more applications of mannitol to the olfactory mucosa can cause permanent channels to be formed between the olfactory cells. While that would allow stem cells ease of access past the blood brain barrier, it also allows other entities past the blood brain barrier, such as bacterial and viruses which can cause bacterial or viral meningitis, which are potentially lethal side effects.