Why do IV infused stem cells end up in the brain?

[Squarepusher]

I'm reading about private clinics that harvest stem cells from adipose tissue and then IV infuse them over many months/years to benefit PwP.

Does anyone know why these cells, delivered systemically, would end up in the brain? The turnover rate for epithelial cells in the gut, for microvilli, and for skin cells is very fast. Why would't these other tissues pull every SC out of circulation given their very large surface area and hunger for new cells?

Has anyone done a C-13 radiolabeled study to see where IV infused stem cells end up? I'm trying to form a picture of why IV infused SCs end up in the nigra striatum of all places

[7springshollow]

I was told approximately %10 of the cells received via IV end up in the brain. They go where the body needs them. You would get more in the brain if you placed them surgically or injected them but you have more risk of serious side effects. Alternatively Hope Bioscience offers a spinal infusion. It is administered via the spine, travels up through the spinal fluid and bathes the brain in stem cells.

[Squarepusher in reply to 7springshollow]

That makes more sense, but I just talked to someone in Hope's trial and the infusion is IV. Different product?

[7springshollow in reply to Squarepusher]

The trial has parameters set by the FDA. It was started using IV and all of the participants have to follow the same protocol or there would be no way to compare . The spinal infusion is available through the right to try program. There is a charge. Hope is not allowed to profit because this is not an approved treatment. They charge only what it costs them to produce the treatment. You would have to contact Hope to find out more. When my trial is completed I plan to try the spinal.

[Squarepusher in reply to 7springshollow]

Thanks for sharing this. I take it they have told you that participating in the IV trial as either placebo or tx does not preclude you from enrolling in the spinal program

[7springshollow in reply to Squarepusher]

They are 2 different programs.

[RonB1 in reply to 7springshollow]

Have you had any reduction/improvement in PD symptoms? Did you have any negative side effects? How many infusions did you get? Thanks

[7springshollow in reply to RonB1]

Hi Ron it's Karen

[RonB1 in reply to 7springshollow]

You again! LOL

[7springshollow in reply to RonB1]

My thoughts exactly 🤔

[7springshollow in reply to 7springshollow]

😂

[Squarepusher in reply to 7springshollow]

Why isn't someone doing this percutaneously? Catheters exist that close off brain aneurysms and those are introduced into the leg (femoral artery). They are pushed all the way up into the brain from the leg

[JayPwP in reply to 7springshollow]

CSF delivery makes sense

[Squarepusher in reply to JayPwP]

What I'm thinking is that an IV infusion center can have eight people treated with one nurse or even a nursing assistant overseeing iV delivery. Because of stem cell loss systemically this is 25-30 treatments. Their direct labor cost is low.

CSF infusion probably or even definitely requires a doctor (?) and a special bed or chair and equipment for monitoring vitals. Higher labor cost. But most cells end up in the brain - so say 6 tx and done

Percutaneous interventional is one-and-done but they need a surgical suite, fluoroscopy, a radiologist, anaesthesoiologist, a neurointerventionalist, assistants etc . No cracking open the head like an open procedure but dissection risk is high and this would be dissection in the arterial side of the brain. I doubt Hope would want to take all this Capex onsite. If something terrible happens can they convert to open? That's a lot of gear to have on hand. I think they partner with a hospital for this

From an FDA perspective option 3 is a drug/device combo product and will take longest for approval

Just thinking out loud if anyone wants to chime in

[7springshollow]

At this point all trial participants have to follow the same protocol. It changes slightly from trial to trial as they discover what works best. Future trials may utilize different methods.

[pdpatient]

 Squarepusher . I explored this question sometime ago and I am left scratching my head. I believe that the stem cells cannot cross the blood brain barrier just like dopamine cannot (or we could just eat a bunch of bananas and we would live happily ever after 😁🤗

The sensible and effective but risky way is to inject directly into the brain.

ucihealth.org/blog/2024/01/...

ncbi.nlm.nih.gov/pmc/articl...

[Squarepusher in reply to pdpatient]

It reminds me of all the people getting $1000+ infusions of NAD, NR, NMN and imagining it going into the brain, or muscle or wherever they wanted it to go and then radio tracer work at Princeton showed that almost all of it ended up in the liver

Not saying that's what's happening here. People who have worked with Hope have excellent things to say and they notice improvements to PD symptoms

[Trig27 in reply to Squarepusher]

exactly

It is astonishing that so many people would rather get an infusion of stem cells, risky, expensive and unproven than exercise, which is healthy, cheap and proven. Make sure you are maximizing exercise before doing the risky stuff.

content.iospress.com/articl...

mdpi.com/1422-0067/21/16/5895

sciencedirect.com/science/a...

[Squarepusher in reply to Trig27]

I agree. Fix sleep, fix exercise, fix distress management and fix diet/constipation first.

[JMDean in reply to pdpatient]

precisely, the blood brain barrier is very effective of blocking this type of elation from outside. It’s the same reason why intravenous glutathione has failed to achieve consistent results (despite its promise as an antioxidant).

[Trig27 in reply to JMDean]

Maybe GlyNac holds some promise here though. Provide more building blocks so the astrocytes can create glutathione.

Also, exercise to reduce ROS: ncbi.nlm.nih.gov/pmc/articl....

[JMDean]

I don’t believe this is an efficacious treatment for PD. If the clinic is unable to provide you with published studies in human beings of their exact approach, I.e randomly injecting cells with the expectation that they will migrate to the needed areas, then I would be HIGHLY suspicious. If you look at the peer-reviewed data in human studies of stem cells over the past 30 years, the only ones that had success were carefully placed in the needed area (and notably, those were fetal stem cells, dissected from the midbrain, not derived from fat or some other unrelated region). This is technically legal but not likely to be helpful for PD and (in my opinion) highly unethical. If you haven’t consulted with your Parkinson’s doctor about this procedure, I would urge you to contact them for their input.

[busters_dad]

l don't think they can pass the blood-brain barrier. But you have many dopamine producing cells in your intestines. Probably one of the many variables of PD is that some people have lost some of these cells and the stem cells replace them.

[kaypeeoh]

Years ago I read a report about stem cells collected from abdominal fat. Everyone knows about stem cells in bone marrow, specifically embryonal cells. But fat contains far more stem cells than an equal volume of bone marrow. Extraction of stem cells from fat is a simple procedure. I treated a dog with an ACL rupture. He was a 90# labrador and dogs that large generally can't be fixed surgically. I filled his stifle with 20cc of stem cells from fat. It seemed to work. Since then I've used the procedure on 20 dogs with ACL or Achilles rupture

In people I've read of this material being injected IV to successfully treat cardiac disease.

But for brain disease medication must be able to cross the BBB. I've heard of stem cells being injected into the brain but haven't heard of any dramatic cures for PD.

[Squarepusher]

Ok, crazy hypothesis that might be worth testing: what if the stem cells don't cross the BBB but repair it over many infusions. Repair it such that environmental toxins are less insulting the brain? Another reason why I think radiotracer studies must be done

[kaypeeoh]

SOME chemicals do cross the BBB. EG, alcohol and cocaine. I had MS. Abnormal white blood cells were crossing the BBB and damaging myelin, the covering on brain cells. When damaged the axons are less able to transmit signals. The treatment was an antibody that could bind to the abnormal cells and prevent them from crossing the BBB. So in theory attaching a molecule to dopamine might make it able to cross. That's just a guess.

But what does help PD is heavy exercise. That stimulates the brain to produce dopamine. Specially more BDNF. But personally being 68 yrs old it's harder to motivate myself to work to near-exhaustion. The studies say 85% of maximum heart rate is needed to push the brain to make more dopamine. That's just three times per week. I'm due for a workout today but haven't done what's necessary to prepare. I'm not in running clothes and haven't had a morning BM. Hopefully the 3rd cup of coffee will kick in and I'll get moving. No pun intended.

[Squarepusher in reply to kaypeeoh]

Thanks, I didn't know it was 85% of max.

[kaypeeoh in reply to Squarepusher]

I read it's 80% to 85% of maximum heart rate. For me that's 136 to 145 beats per minute. I Set my treadmill to 15% grade and 12 minutes per mile pace. I shoot for 30 seconds sprinting with 90 seconds recovery done eight times.

[Squarepusher]

I try to do my workouts with nasal breathing only. It seems to me if the metabolic demand from muscles is constant and the volumetric flow rate of O2 is restricted then the only thing the body can do to compensate is increase heart rate.

Flow rate is proportional to the 4th power of diameter. Now that I think about it that's true for an incompressible fluid, but I'm not certain about a compressible fluid like air