I’ve had a few patients e-mail and ask if they should have a doctor place stem cells up their nose to treat a brain injury. While we don’t treat neurologic diseases, like ALS, dementia, or MS, they trust our expertise. Hence, today I’ll tackle the issue of intranasal stem cell delivery.
Brain Stem Cells: How to Get Stem Cells to the Brain?
Getting stem cells to the brain to treat diseases like ALS, dementia, or MS is a sticky problem. Why? First, if you inject them through a vein (intravenous, or IV), almost all won’t make it across the blood-brain barrier (BBB). To learn more about that issue, watch my video below:
If only a few cells will make it to the brain if we inject them IV, what are other possibilities? One might be injecting them into the spine. There are two types of injections that would be possible—epidural and intrathecal. Epidural would place the cells outside the space that communicates with the brain. Intrathecal means injecting into the dural sac, which is a space that connects with the ventricles of the brain. Hence, stem cells injected here could make it physically into the brain, but the BBB still separates them from the brain tissue. You could also float a catheter and inject cells into the arteries in the brain, but then the BBB is also in the way. Finally, there’s always drilling a hole in the skull, but for obvious reasons, if there’s an easier way to get cells into the brain, this should be avoided.
BBB, in This Case, Doesn’t Stand for Bigger Better Deal
BBB is the Blood-Brain Barrier, which is a big problem for getting anything into the brain. The purpose of the BBB is to keep things, like foreign bacteria, out of the brain. So it’s particularly good at keeping cell-sized things from making it to the brain tissue.
One of the ways that has been proposed to open the BBB “gate” is using a drug called mannitol. This drug can increase the permeability of the BBB and in experimental rat studies has been shown to produce better results when stem cells are injected into the jugular vein than when the drug isn’t used. However, the researchers postulated that this wasn’t because stem cells were making it across the BBB, but maybe some of the chemicals that the stem cells produced made the trip. Another study looked at the idea of whether using mannitol (a sugar) with a chemotherapy drug called temozolomide would further increase the BBB permeability. This combo also seemed to improve the effectiveness of IV stem cell treatment in rats. Again, this likely happened due to the small particles the stem cells produced making it to the brain rather than the stem cells themselves in this method of brain stem cells delivery. The same thing happened in this animal study with mannitol only, so there certainly seems to be something to the idea of using mannitol to help IV stem cells work better, even if that’s not happening because the stem cells themselves are making it across the BBB.
Stem Cells up the Nose?
The idea of putting stem cells up your nose just sounds gross. However, the idea has some roots in anatomy. You may remember as a kid someone telling you that some secret agent or an army special ops guy could kill someone by fracturing their nose up to into their brain. Or maybe you’ve never heard of that and I just had a twisted childhood? Either way, the roof of the nasal cavity and the brain are very close together (see video at the top of the page). In fact, there’s only one thin bone separating the two. This is called the cribriform plate.
This anatomical fun fact has led to the idea capitalized on in modern drug delivery that intranasal sprays can get chemicals to the brain. For example, we now have intranasal insulin, steroids, antiasthma medications. Hence, the main idea is sound.
A Study on Intranasal Delivery of Stem Cells
A recent research investigation set out to answer the question of whether stem cells delivered intranasally in rats and a primate-like model would end up in the brain. The researchers labeled the cells so they could be tracked, and after the therapy, they dissected out the brains to see where the stem cells went. What did they find?
Most of the stem cells ended up staying in the nasal cavity. Some did make it across the thin bone and into the brain area, but most of those were found in the olfactory bulb part of the brain that’s located at that spot. While a few stem cells ended up in adjacent areas of the brain, none ended up making it into the parts of the brain where these big diseases happen.
The upshot? Can you put stem cells up the nose to treat diseases like dementia? Likely not. That isn’t to say that chemicals produced by the cells might not help the brain. However, the idea that stem cells can be delivered this way needs to be much better dialed in before you can hang your hat on this delivery route.