234 replies to this topic

[resveratrol_guy]

So I'm planning to get stem cell therapy in the near future. In particular, BMSC (bone marrow stem cell) transfusion from the iliac crest (side of hip) to general circulation via reinjection. For the moment, I'm not going to reveal the center where I will be conducting this procedure. Suffice to say, I am well aware of the stem cell con shops out there, and this place is definitely not one of those clown operations (unless you believe that stem cells in general are snake oil).

I started this thread for 2 purposes: (1) to seek feedback on my current pre- and post-treatment plan and (2) to submit my experience for social benefit, in the hopes that it will accelerate some of the statistical analysis that has been so weak in this field, largely on account of the dearth of trials, whether properly controlled or not. As stem cell entrepreneur Peter Nygard said, "[If] you risk nothing, you risk everything!" And as Steve Jobs said, "You are already naked." In other words, you are already taking risk just by virtue of being alive. The question is not whether or not one will eventually die, but whether or not one will actually live in the interim. With this philosophy in mind, here is why I am going to do this (after months of research):

My problem:

I had a series of neurological and digestive failures in 2013, particularly in August and September due to massive psychological stress. There is still debate among the doctors as to exactly what happened and why, but the bottom line is that while I've been scanned with multiple imaging modalities and had many blood tests, no cancer is in evidence. However, it is clear from my symptoms that I still have (1) some residual mental deficits, particularly in terms of maintaining attention and converting short term to long term memory, somewhat supported by MRI showing enlarged ventricles (cerebral atrophy) and a marble-sized nonspecific inert lesion (stable over 7 months, and suspected to be either a congenital fluidic void or the dead zone induced by a previous stroke) and (2) impaired digestion which requires enzyme supplementation, despite pancreatic pathology being categorically ruled out. I also suffer from hyposmia, although that was due to a bacterial infection contemporaneous with the onset of the other symptoms. I do have small benign hemangiomas in the liver, but mutliple scans have not raised concerns of future malignancy, although it's possible.

But my main problem is the same as yours: aging. I think the additive cancer risk of BMSC therapy is actually negative: longterm enahanced tissue perfusion and functionality outweigh the risk of a transient spike in growth factors. NOTE: This is NOT the same as induced pluripotent stem cell therapy, somatic cell nuclear transfer therapy, or adipose stem cell therapy, which exhibit different risk/benefit profiles. It's also not proven in any conventional sense; it's my own conclusion from examining a number of studies.

My recovery thus far:

I have done pretty much everything known to conventional science to substantially improve mental function. I started out with a 25% (twenty-five) memory ranking on Lumosity, which has been brought up to 91% (ninety-one) as of today. LPI started somewhere in the 30-40% range and is currently 87% (same computer and Internet connection, same time of day, same "I like it" answer to all game feedback questions, no practice between workouts, no studying third party techniques to raise my score, always at least 8 hours since anything but water consumed). For the record, I take these daily: 250 mg resveratrol (obviously), vegetable juicing (varies, now average just a few ounces a day), high intensity short duration exercise (10 minutes at 15% incline and 60% maximum cadence on treadmill or similar outside run), a multivitamin (Centrum men's), vitamin D (1000 IU), quercetin (500 mg) with bromelain (150 mg) ("Super Quercetin"), pterostilbene (eyeball about 200 mg), shiitake maitake extract (previously 1/3 capsule daily, down to 1/3 every 3 days or so due to brain overdrive), an egg, a teaspoon of white chocolate chips (for phosphatidyl serine in the soy lecithin, probably useless but who knows), a half pint of blueberries (varies), and most recently carbon 60 olive oil (c60oo) (just under a teaspoon, about 3 mg). The only "medicine" I take is protonix to shut off acid production and sertraline to mitigate excessive stress; this duo has had profound effects on my physical and mental health, despite being conventional (and heavily overprescribed) drugs. Lumosity itself has probably imparted some significant benefits as well. (Brain games are not much better than just browsing the Internet for the same amount of time each day, but that's not the same as saying they're ineffective at improving brain function, as some have erroneously claimed.)

As you can imagine, I was not exactly happy with a 25% memory performance ranking vs age group peers, when I actually used to be "smart". To give you an idea of what this means in practice: just 4 months ago, I had to plan carefully and think very hard just to figure out how to hang a fluorescent light under a cabinet, despite having the instruction manual in front of me. Now, I can see the entire process in my head, despite not having installed one since then. The quantitative improvements in my mental performance have vastly exceeded what I was led to believe was possible by my neurologist. The thing is, I made the mistake of not paying attention to my Lumosity peer ranking, instead just focussing on their rather meaningless score. At the time I started, my dream was just to be average again. I hoped that I could reach 50% memory and 50% LPI. But I studied this forum and employed literally everything that my neurologist recommended, knowing that it would make probably a 20% difference because neurology is a thankless profession of meager successes.

 

Maybe I was wrong. Seriously wrong. So now, I'm actually starting to like this. I want more, without becoming an egomaniac in sense of Lawnmower Man (a cautionary allegory of neurological hyperdevelopment perverted into intellectual narcissism). I am aware that this therapy might literally kill me a few years hence, but certainly not in vain. This is worth trying. I want to be as productive as possible in my life. I do not want to be someone else's burden, even if that would afford me many extra years. If it all goes wrong, then at least the next guinea pig will know what not to do.

Next steps (where I really need your suggestions or criticisms):

1. In addition to existing antiangiogenic supplements, add indol-3-carbinol to jackhammer down metastatic pathways. Limonene from juiced lemons with the peel still attached is also helpful, but I can't get too much on account of my stomach issues. The idea is to prevent any pathological stem cells from deciding to form tumors, particularly in the first month when about 50% of the longterm recovery seems to occur. (I've heard that, despite their antiangeogenic and proapoptotic properties, resveratrol (and presumably pterostilbene) actually aid stem-cell-mediated rejuvenation including revascularization (thoughts?).

2. Get BMSC injection. Based on previous patient data, the estimate we're looking at is 250 million stem cells. That's on the high side (logarithmically), the most I've ever heard of in a single therapy session being a billion, while the smallest that seemed to be clinically effective was in the range of 4 million delivered within hours (as opposed to a year) of brain injury.

3. Minimize stress. This implies allowing my Lumosity scores to decline for a couple months as my nascent blood vessels mature, in the relative absence of exercise. I plan to work back to full intensity after 2 months.

4. Once revascularization has initiated a few days after therapy, start taking nerve growth factor eye drops and/or Lion's Mane mushroom extract to upregulate neurogenesis. (I don't want to take this before revascularization, because it might generate neurons that can't be properly nourished, and therefore become pathological.)

5. Maybe get hyperbaric oxygen therapy, to allow deeper revascularization and reneuralization. But this could also be a mistake because (1) the money might be better spent on a future round of BMSCs and (2) I do not want my neurons becoming dependent upon excessively oxygenated conditions which do not represent their normal operating environment.

6. Depending on further research, start taking dihexa to explode the population of axonal connections.
 

Yes, I know I'm insane. But that only proves that I need to do what I'm proposing to do.

 

Suggestions? Cautions? Thoughts?

 

The following evidence, althought not independently convincing, is nonetheless compelling with regards to the hypothesis that clinically significant brain revascularization is possible, even at advanced age. (The Indian paper involved BMSCs; the video is, I believe, the work of Zannos Greckos and uses adipose stem cells -- hopefully with the same amount of the same dye injected in both images). Yes, it might all be Photoshop (but why, when there are easier ways to sell snake oil?), so take these with a grain of salt:

 

http://omicsonline.o...633.1000129.pdf

 

 

Edited by resveratrol_guy, 06 September 2014 - 05:04 AM.

[ceridwen]

I wish you would tell us where you are thinking of getting help for others in desperate situations

[resveratrol_guy]

I wish you would tell us where you are thinking of getting help for others in desperate situations

 

That's a reasonable request, and entirely in tune with my social values. I don't wish to disclose the name of the center in advance of the procedure for various reasons which support both privacy and good science. However, I do indeed plan to disclose that after the fact, which in my estimation should be November at latest. Bear in mind, the longterm risks and benefits of BMSC therapy are for the most part based on extrapolation of short term trends, so the only thing I will know for certain afterwards is the quality with which they executed the procedure. Some early benefits and side effects may be in evidence as well. I will report back here as appropriate.

[Logic]

I wish you would tell us where you are thinking of getting help for others in desperate situations

 
That's a reasonable request, and entirely in tune with my social values. I don't wish to disclose the name of the center in advance of the procedure for various reasons which support both privacy and good science. However, I do indeed plan to disclose that after the fact, which in my estimation should be November at latest. Bear in mind, the longterm risks and benefits of BMSC therapy are for the most part based on extrapolation of short term trends, so the only thing I will know for certain afterwards is the quality with which they executed the procedure. Some early benefits and side effects may be in evidence as well. I will report back here as appropriate.

Ceridwen has Alzheimer's and in his words is 'fading fast', so you may want to make an axception and PM him.

[niner]

Ceridwen has Alzheimer's and in his words is 'fading fast', so you may want to make an axception and PM him.

 

I'm pretty sure that's a self-diagnosis without benefit of a medical exam.  Ceridwen has something, but I don't think it's Alzheimer's.

[Logic]

Ceridwen has Alzheimer's and in his words is 'fading fast', so you may want to make an axception and PM him.

 
I'm pretty sure that's a self-diagnosis without benefit of a medical exam.  Ceridwen has something, but I don't think it's Alzheimer's.

True Niner

something is causing cognitive decline, but from looking at is posts I would go and see a doctor if was him.

Soz for hijacking your thread resveratrol_guy.
I will be watching this thread with interest.

[resveratrol_guy]

 

 

Ceridwen has Alzheimer's and in his words is 'fading fast', so you may want to make an axception and PM him.

 
I'm pretty sure that's a self-diagnosis without benefit of a medical exam.  Ceridwen has something, but I don't think it's Alzheimer's.

 

True Niner

something is causing cognitive decline, but from looking at is posts I would go and see a doctor if was him.

Soz for hijacking your thread resveratrol_guy.
I will be watching this thread with interest.

 

 

Ceridwen, please send a link to my post here to a friend who can help you to find treatment.

Obviously, anyone with dementia symptoms should start with a visit to a neurologist. I would also study the Nootropic section here (especially Lion's Mane), with careful attention to the reports of long term users in all cases. And while I have not seen it mentioned here, I would Google "alzheimers coconut oil" and consider replacing junk food calories with coconut oil. That, and seriously consider taking dihexa, which has apparently reversed Alzheimers symptoms in rodents (but is untested in humans and might not be safe).

 

http://www.longecity...ootropic-stacks
http://www.alzheimer...-for-alzheimers
http://www.longecity...ation-as-dihexa
http://www.longecity...ction-and-risks
http://www.longecity...is-co-organizer

I can also provide the following links which relate to the topic at hand, i.e. stem cell therapy for brain damage. The best we can conclude from them is that they point to the need for further study. Of course, "further study" is not applicable to anyone in a desperate situation. In such cases, unfortunately, one must decide whether or not to take significant risk in order to attempt clinical improvement. While the stem cells themselves are obviously the overriding consideration in the success of stem cell therapy, one must also take care to select a team with a proven track record of successful procedures (at least, in the sense of operating room practices, nevermind longterm results), in addition to careful consideration for the exact type of therapy applied.

I can neither endorse nor discredit any of the following, except to say that each link is worth more serious investigation to anyone who has increasing dementia symptoms.

Note: do not assume that claims of "results within minutes" are all placebo. These ultra short term benefits may be due to injected stem cells secreting antiinflammatory agents as described here: "Mesenchymal stem cells decrease pro-inflammatory cytokine expression [25-26], and secrete anti-inflammatory agents, including interleukin 1 receptor antagonist, interleukin-10, and prostaglandin E2". Granted, indirect brain stem cell therapy via intravascular (as opposed to intracranial) injection seems to reach 50% effectiveness only after a month or more.

Stem cells for stoke at Stanford University (@ 1:45). The same technique, but targetted at the hippocampus, might well ameliorate Alzheimers:



Potentially verifiable brain revascularization story. (I believe this is the lady whose brain is in the video I posted above):

http://www.prlog.org...e-dementia.html

Long term outcome of stem cell patient with severe dementia (not in English, but interesting nonetheless). This lady was apparently treated at XCell in Germany, which was later shut down as a result of patient deaths and management malfeasance (links below video). But let's not throw the baby out with the bathwater here. Reckless individuals are often the first to discover successful therapies because they have no concerns for patient welfare so, perversely, they might have been onto something which would be therapeutic under more controlled circumstances:

 

http://www.ipscell.c...des-new-details

http://www.telegraph...th-of-baby.html

 

Note on the IPSCELL link: I think the popular "Knoepfler Lab Stem Cell Blog" is an example of good scientific skepticism which is nonetheless socially deleterious. The author's sole objective seems to be to show that stem cell therapy: is statistically worthless in the sense that noisy-data-equals-zero-data -- pseudoscientific arrogance refuted by math but reinforced by overpriced universities, so we can wait for someone's "esteemed colleague" to give us a narrower statistical distribution which suddenly constitutes "proof"; is automatically unsuccessful if the doctor administering it had shady financial dealings; and that we should all wait til a century after we're dead, so that the "right" therapy will finally have FDA approval. Yes, less certainty implies greater danger, but the passage of time itself is dangerous; hence there is some optimal tradeoff between the two, which I don't pretend to be able to calculate, but surely it's not simply a matter of waiting for "good" science without regard to the prospective timeline. We need to stop associating maximum clinical benefit with maximum certainty. This is pompous, counterproductive, and smacks of science-by-credentials instead of risk analysis.

 

Animal study at the University of California involving hippocampal injections:



A religious leader with Alzheimers treated with reportedly great success (umbilical cord stem cells -- teratoma risk?). But he later died (second link). Perhaps contacting members of his organization (third link) would reveal more details as to both issues, and whether or not they are likely related. (Regardless of what you might think of his religious philosophy or Dr. Rader's infomercialistic Stems Cells of America, the stems cells might have worked.)

http://stemcellofame...s-patient-srila
http://harmonist.us/...rayana-maharaja
http://www.purebhakt...i-maharaja.html

CBS series on stem cell fraud:

http://www.cbsnews.c...tion-26-08-2012

And for everyone here, I remember what it was like to have dementia. (I feel very fortunate to be able to use such a rare grammatical construction.) For those of you who have never had the experience, it's not the uniform dulling of cognitive function that you might expect. There are cerebral functions that persist more strongly than others. In my case, for example, my vision remained excellent. But I had trouble navigating simple buildings, even after taking the same route many times. And while I understood the words that were said to me, individually, I needed to take a few seconds to assemble what they implied as an interwoven linguistic whole. When paying for my groceries, I would stand there at the cash register, waiting to be prompted for what to do next. The cashier would need to tell me to swipe my credit card, then push the "OK" button, then sign. Now, I can talk to my friend while swiping my card and still remember to check my receipt to make sure I wasn't overcharged. "Surreal" doesn't begin to describe the whole ordeal and subsequent recovery. At this point, I'm attempting to subvert my last significant deficits to stem cell technology, and hopefully, maximize my mental capability as any humanist would naturally desire. Perhaps the part of my brain which espouses mediocrity and risk aversion as a survival strategy has been irrevocably damaged, in which case, good riddance.

 

Edited by resveratrol_guy, 08 September 2014 - 04:54 PM.

[John Schloendorn]

bone marrow stem cell

 

 

Not sure what that might be.  If someone can get a hold of 250 million of them, then we can be certain that it's not the same cell that's traditionally seen as the active ingredient in a bone marrow transplant (the hematopoietic stem cell).  My guess is, it would have to be some kind of adherent stromal / SMC / adipocyte like cell, that was re-named into "stem cell" in recent years because it sounds cool and sells better.    Are any further characteristics of the cell known?  How do they get the cell?  From you, or from a donor?  How do they know that whatever they harvested is a stem cell, and how do they count the 250 million out? 

[resveratrol_guy]

 

bone marrow stem cell

 

 

Not sure what that might be.  If someone can get a hold of 250 million of them, then we can be certain that it's not the same cell that's traditionally seen as the active ingredient in a bone marrow transplant (the hematopoietic stem cell).  My guess is, it would have to be some kind of adherent stromal / SMC / adipocyte like cell, that was re-named into "stem cell" in recent years because it sounds cool and sells better.    Are any further characteristics of the cell known?  How do they get the cell?  From you, or from a donor?  How do they know that whatever they harvested is a stem cell, and how do they count the 250 million out? 

 

 

Yeah, cell type and count is an important consideration, if for no other reason than the maintenance of therapy standards. "Autologous bone marrow transplant" might be more accurate nomenclature than "bone marrow stem cell therapy", even though of course the stem cells are what we're interested in. It seems that the usual practice is simply marrow mining of the hip (producing 100 mL or more of marrow) followed by reinjection, so in this sense we're getting whole marrow. There seems to be some crude filtering involved, but I think this is just to guard against foreign debris, not to select cell types. I have not found any anecdotes which provide more detail than that. Therapists seem to talk in terms of "cells" for example, Neil Burton's 1.6 billion "cells" at http://stemcellsjourney.blogspot.com . But in some cases, these have been (incorrectly?) reported as stem cell counts. The exeception is clinical trials of specific cell types, which are generally rigorous in the sense that they modify, replicate, and inject one specific cell type in an accurately determined quantity.

 

So this all raises an important question, which is that the hundreds of millions of oft-reported stem cell counts as typical therapeutic injection quantities might not be comparable in any useful way to the single millions of definitely-stem cells injected in various clinical trials, for example, Neuralstem for spinal regeneration. Perhaps the former number is gross marrow cell count, of which some small fraction are actual stem cells. In fairness, it might also be that most therapists are claiming exactly that, but somehow "cells" become "stem cells" in the reports of patients who conflated the concepts. So I may well be mistaken in my assumption that we're talking about hundreds of millions of stem cells.

 

As much as this matters for good science, what is the pragmatic significance? Do we know enough about how much marrow is too much or too little in order to make a reasonable attempt at dosing advice? In other words, if this therapy is likely useful, then is a billion worse than a hundred million? The only (major) hazards I can think of are: (1) replication stress, as the other thread here mentions, which means that extracting bone marrow invokes replication to replace it, which is certain to introduce some degree of genetic error and (2) spleen overloading with the massive spike in immune cells. I'm tempted to mention pathological angiogenesis, but again, I think this is outweighed by enhanced tissue perfusion with new blood vessels, in that the most dangerous cancers seem to love hypoxia (and most cancers generally -- thanks, Mr. Warburg -- if we look at the well established link between sleep apnea and cancer).

 

But thank you for raising the issue. This is surely important, and perhaps I should tell my therapist to stop at 50 mL or whatever. The problem is, I don't know what level is optimal. If anyone has a numerical grasp of this, then please enlighten everyone.

 

Small side note related to the original post: I have small blind spots in both eyes, mainly the left. They seem to be floaters, and do indeed migrate, but never really go away. It's been that way for several months. I don't see how my proposed therapy is going to fix that, but I thought I should mention it in case there's some improvement. Also, L4-L5 spinal disc degeneration confirmed on MRI, with chronic low-grade back pain. And finally, bilaterial tinnitis which seems to be aggravated by eating a lot of protein -- a constant "eeeeee" in my ears, ranging from barely perceptible to annoying enough to keep me awake.

 

Edited by resveratrol_guy, 09 September 2014 - 12:50 PM.

[resveratrol_guy]

I'm still working out exact dates (which is nontrivial on account of the logistics), but the schedule is looking like October, so I'm still trying to get a Lumosity brain baseline. I know I've said this before in the c60oo thread, but I really think 89% Lumosity performance index peer ranking (79% speed, 93% memory, 80% attention, 85% flexibility, 89% problem solving) is the best I can muster without physical brain rejuvenation. Screen shot attached. I had plateaued at 79-80%, but c60oo has been outrageously beneficial in breaking that logjam, hence the delay in reaching baseline. Anyway, I suspect this is the peak because, for one thing, my fingers are starting to misexecute commands, resulting in wrong keys being pressed during speed tests, which is a new limitation that I had not previously encountered.

 

BTW as to the accuracy of these numbers, Lumosity only just today released a personalized report. The objective of the report was to determine, based on my best 10 games (out of 40 available), the professions whose practitioners had the most in common with me. The system correctly indicated that my brain most closely matched those of mathematicians, which any human who knows me could reasonably have concluded. I've discussed other strengths and weaknesses of the system at the thread linked above.

Attached Files

•  lumosity2.png   42.47KB   10 downloads

Edited by resveratrol_guy, 10 September 2014 - 02:23 PM.

[Logic]

Also, L4-L5 spinal disc degeneration confirmed on MRI, with chronic low-grade back pain.

http://www.longecity...424#entry686424

[Flex]

Dont expect miracles and especially; dont expect new brain cells.

I couldnt figure out whether the Stanford guy used Bonemarrow cells, so I´m still sceptic.

 

It could be helpful via growth factors, Vascular factors & etc.

because when the injected cells die, they release those factors which strenghten Your body- and braincells.

But You can mimic this vascular factors partly with Cerebrolysin.

http://www.scienceda...30131084614.htm

 

This is based on my own investigation. Therefore I cant guarantee anything.

 

Regarding Ceridwen:

Better wait untill she went finally to a Doctor and got finally a MRI

until then, as niner said, its a self diagonsed speculation.........

Because (certain) Depressions, Parkinson, Psychosis and so on, do also cause memory problems !

 

Edited by Flex, 15 September 2014 - 02:28 PM.

[resveratrol_guy]

Dont expect miracles and especially; dont expect new brain cells.

I couldnt figure out whether the Stanford guy used Bonemarrow cells, so I´m still sceptic.

 

It could be helpful via growth factors, Vascular factors & etc.

because when the injected cells die, they release those factors which strenghten Your body- and braincells.

But You can mimic this vascular factors partly with Cerebrolysin.

http://www.scienceda...30131084614.htm

 

This is based on my own investigation. Therefore I cant guarantee anything.

 

Regarding Ceridwen:

Better wait untill she went finally to a Doctor and got finally a MRI

until then, as niner said, its a self diagonsed speculation.........

Because (certain) Depressions, Parkinson, Psychosis and so on, do also cause memory problems !

 

On the one hand, I do not expect new brain cells to directly result from the injection (unless the cells can somehow cross the BBB and differentiate into neurons, which I don't presently expect). However, I do expect to acquire a net gain in neurons (not sure about astral cells, pyramidal cells, and others) in a matter of months following therapy. The reason is that new vasculature will be able to support more cells, by virtue of better nutrient delivery (especially O2) and waste disposal. So once I get my exercise regimen back on track following a break for therapy, I expect to keep more of my daily neuron profit from otherwise ordinary hippocampal neurogenesis. Of course, I intend to continue my existing supplements which help keep my existing neurons alive (e.g. c60oo). Beyond this, I have a laundry list of other supplements to try in due course over the next year.

 

Your comment regarding cerebrolysin is very relevant here, although it's apparently expensive compared to alternatives. I have studied it in some detail and I know someone who benefitted from it. It's on my list. My understanding is that it comes from the brains of pig embryos, which is obviously not as desirable as a synthetic compound and at least in theory carries some risk of CJD (human prion disease). All in all, it's worth serious analysis.

Your theory, which I haven't heard before, that stem cell death actually creates a beneficial release of growth factors is interesting. I wonder how much of their benefit comes from normal growth factor secretion as opposed to postmortem release. This is one for the researchers.
 

[ceridwen]

Flex I went to my Dr at the first sign of trouble. It took them almost a year to get around to considering giving me an MRI.

[ceridwen]

Cerebrolysin is not available in the UK.

[ceridwen]

@@reservatrol_guy my symptoms are quite different from your account of dementia but everyone has different strengths and weaknesses and that is reflected even here. I have tinnitus when it's loud I feel like I'm dissolving. I have lost a massive amount of feeling in my body. I began hoping it was MS so I wouldn't have to die. I did not think I would ever say that.

Edited by ceridwen, 16 September 2014 - 05:54 AM.

[ceridwen]

Reservatrol_Guy how are you going to get the BMSC injection? I'm fighting for my life and I wondered.....

[niner]

Flex I went to my Dr at the first sign of trouble. It took them almost a year to get around to considering giving me an MRI.

 

Your doctors apparently don't think that your death is imminent.  What is their diagnosis?

[Flex]

 

 

On the one hand, I do not expect new brain cells to directly result from the injection (unless the cells can somehow cross the BBB and differentiate into neurons, which I don't presently expect). However, I do expect to acquire a net gain in neurons (not sure about astral cells, pyramidal cells, and others) in a matter of months following therapy. The reason is that new vasculature will be able to support more cells, by virtue of better nutrient delivery (especially O2) and waste disposal. So once I get my exercise regimen back on track following a break for therapy, I expect to keep more of my daily neuron profit from otherwise ordinary hippocampal neurogenesis. Of course, I intend to continue my existing supplements which help keep my existing neurons alive (e.g. c60oo). Beyond this, I have a laundry list of other supplements to try in due course over the next year.

 

Your comment regarding cerebrolysin is very relevant here, although it's apparently expensive compared to alternatives. I have studied it in some detail and I know someone who benefitted from it. It's on my list. My understanding is that it comes from the brains of pig embryos, which is obviously not as desirable as a synthetic compound and at least in theory carries some risk of CJD (human prion disease). All in all, it's worth serious analysis.

Your theory, which I haven't heard before, that stem cell death actually creates a beneficial release of growth factors is interesting. I wonder how much of their benefit comes from normal growth factor secretion as opposed to postmortem release. This is one for the researchers.
 

 

 

There is no proof that bonemarrow stemcells turn into neurons.

Or why do they need to be converted into stemcells ?

http://www.scienceda...30422154756.htm

 

Those Scientists of the mice experiment, have likely used real stemcells.

They improvements are likely caused by growthfactors and revasculation, as stated in the Indian paper.

An increase in "neurogenesis" could also be caused just by stimulation of the SVZ or Hippocampal stemcells so it can be stated as such afterwards.

 

But even the SVZ seems according to a new finding not be able to serve new braincells in Humans.

 

Just read this article, they state that there are no new cells !

http://www.theguardi...apy-pilot-study

Cerebrolysin is expensive, but Bonemarrow therapy is by far expensiver

Try Your Luck, but there shouldnt appear siginficant enough new cells to be responsible for any improvement,

but via Synaptic plasticity and new vessels

So ask You self why quadriplegics are not treatable by BMS cells.

 

Btw, even Astrocytes do not regrowth.

[resveratrol_guy]

There is no proof that bonemarrow stemcells turn into neurons.

Or why do they need to be converted into stemcells ?

http://www.scienceda...30422154756.htm

 

Those Scientists of the mice experiment, have likely used real stemcells.

They improvements are likely caused by growthfactors and revasculation, as stated in the Indian paper.

An increase in "neurogenesis" could also be caused just by stimulation of the SVZ or Hippocampal stemcells so it can be stated as such afterwards.

 

But even the SVZ seems according to a new finding not be able to serve new braincells in Humans.

 

Just read this article, they state that there are no new cells !

http://www.theguardi...apy-pilot-study

Cerebrolysin is expensive, but Bonemarrow therapy is by far expensiver

Try Your Luck, but there shouldnt appear siginficant enough new cells to be responsible for any improvement,

but via Synaptic plasticity and new vessels

So ask You self why quadriplegics are not treatable by BMS cells.

 

Btw, even Astrocytes do not regrowth.

 

 

"Functionally, the superior blood flow in CD34+ treated rats was associated with a vast improvement of both motor and behavioral endpoints, when compared with control rats treated with saline. The injected CD34+ cells were found to differentiate into endothelial and glial cells, as well as neurons, which again emphasized the inherent stem cell capacity of CD34+ cells." So I'm starting to learn that the real heroes here are CD34+ cells -- a small minority of whole bone marrow cell populations -- as expounded in this 2011 metastudy by the Texas Heart Institute (which explores stroke as well as myocardial infarction). This is probably the best summary I've ever read on this issue, and it's kind of ridiculous that we actually knew this much in 2011, but progress has been minimal since then, largely on account of low patient enrollment in various trials. Anyone considering stem cell therapy needs to read this paper.

 

https://www.ncbi.nlm...cles/PMC3231531

 

Having said that, I'm not actually looking to stem cell therapy to give me new cells, apart from endothelial cells, which I think is well within the implications of existing research across a wide variety of organisms and injury sites. So in other words, I'm anticipating increased secretion of growth factors. With better vasculature, organs function better. Yes, there is a cancer risk, but I don't see good evidence from any study that the net impact on lifespan is negative. More vasculature also means more immune access to deeply buried cells which might otherwise go rogue undetected. (For safety's sake, readers need to remember that we are talking about reinjecting one's own bone marrow or some fraction of its components -- not one's own umbilical cord blood, not adipose stem cells, and certainly not stem cells from another person, which carry very different risk profiles.)
 

The SVZ is most active with respect to neurogenesis during periods of falling in love. I don't expect stem cell therapy to improve my romantic life (now there's a research proposal!), so I don't expect many new neurons there. I do expect my hippocampus to keep cranking them out (just like now, as an exercise response) although (1) it will produce fewer of them for the first several weeks after therapy, while I mostly rest and allow new blood vessels to form (probably resulting in a temporary decrease in Lumosity scores) and (2) I don't expect any meaningful increase in the rate of neurogenesis after the fact, but I do expect that neovascularization will allow me to get more out of the ones that I already have and those which I generate in small numbers every day.

 

So in effect, you are correct as far as I can see: neurogenesis due to BMSC therapy is not zero, but is negligible relative to the observed benefits, most of which are probably driven by growth factors like VEGF. That's fine with me. I just want to get smarter, by whatever means I can muster.

 

I definitely agree that cerebrolysin is worth a look. I understand the point about minimizing cost first. But in this case, I think it's important to do stem cell therapy while I still can, with surely much more impact than it would have once I'm much older. Ideally, I want to get the body functioning as well as possible first, so I can take maximum advantage of nootropics later, instead of looking to nootropics as some sort of bandage to compensate for a system that's more rapidly falling into disarray. So I will revisit cerebrolysin after the fact.

 

HOWEVER... here's the conclusion I'm coming to, after all this research (seems like the science is evolving so rapidly that I need to read this forum and other sources every day): Neopogen (filgrastim, granulocyte colony stimulating factor, GCSF) is a much better way to go than outright bone marrow aspiration. Why? Because whole bone marrow contains mononeuclear cells (MNCs) which are somewhat beneficial, but also have some deleterious effects according to the paper above (not sure of the specifics). Presumably, there are other cells in it as well which are irrelevant to the healing process and may just cause havoc. OTOH neupogen is a CD34+ mobilizer; it forces them to leave the bone marrow and enter the circulation. A small percentage of people are nonresponders, but otherwise a few injections of this drug can add hundreds of millions of CD34+ cells to the circulation in a matter of days (yes, stem cells, not just "bone marrow cells").

 

Historically, Neupogen has been used for cancer patients -- not to regenerate damaged tissue, but to enhance immune function during the stress of chemotherapy. For this reason, and because the drug is too new to warrant its use for general-purpose rejuvenation, I think it may well have undocumented benefits.

 

So I'm thinking of shifting my therapy strategy to drug-induced CD34+ mobilization. I've proposed a therapy plan to the center, and they said they'd get back to me next week. Sorry this is taking so long. I have no desire to delay the process, but as you might expect, this is rather more complicated than a simple injection might suggest, not to mention the legal and logistic annoyances.

 

NOTE: Neupogen increases the risk of leukemia. I read a study on this and the numbers did not scare me, relative to the risk of doing nothing to improve my vascular health. But do your own research, and be advised that my proposed use is utterly off-label.

 

Having said that, if anyone sees some other danger or defficiency in this proposed approach, then speak up because you might benefit everyone here.

 

Ceridwen: I am quite sympathetic to your plight. But what we all need is more details about your condition. A diagnosis would be ideal. But blood tests, MRI results, or other data could be useful as well. I think your desparate condition deserves its own discussion thread, but I have no problem if you want to post here. I'm confident that this community is brilliant enough to suggest some reasonable therapies if in fact you can provide them with good data. If you want to follow me in the Neupogen direction, that's your choice. It might actually help you. But I'm in no position to endorse this course of action in your case.

 

Edited by resveratrol_guy, 17 September 2014 - 04:01 PM.

[Flex]

Afaik Mice stem cells behave different than the humans i.e. migrate through the entire brain.

( couldnt find the paper in a trice)

The question still remains why Bone marrow stemcells or other !

dont work in quadriplegic people.

 

Btw:

Human and monkey striatal interneurons are derived from the medial ganglionic eminence but not from the adult subventricular zone.

http://www.ncbi.nlm....pubmed/25223700

 

Thats all. I dont care anymore

 

[resveratrol_guy]

Afaik Mice stem cells behave different than the humans i.e. migrate through the entire brain.

( couldnt find the paper in a trice)

The question still remains why Bone marrow stemcells or other !

dont work in quadriplegic people.

 

Btw:

Human and monkey striatal interneurons are derived from the medial ganglionic eminence but not from the adult subventricular zone.

http://www.ncbi.nlm....pubmed/25223700

 

Thats all. I dont care anymore

 

So if you're right about mouse stem cells being more migratory than their human counterparts, then I agree with your implicit point that mouse studies aren't particularly informative with respect to the prospect of human mental improvements resulting from systemic stem cell therapy, to the extent that they depend on neurogenesis. But as I explained above, I think the evidence is that neurogenesis is a secondary issue insofar as clinical benefit is concerned.

 

As to quadraplegics, I don't think we can say that bone-marrow-derived stem cells don't help. It depends on the reason for which one is quadraplegic, for instance, a stroke vs. a spinal injury. In the former case, the Stanford video above shows a woman who is now able to raise her arm over her head after therapy, which had been essentially disabled before the fact; there's no reason to expect that similar results would not be possible, given a patient with strokes in the right locations to disable all 4 limbs in a similar manner. But in the latter case, it's quite clear that stem cells are at best of minimal utility because the damage is in an area of the CNS which is essentially devoid of vasculature in comparison to the brain itself. So there's no way that neovascularization could improve oxygenation, nutrient delivery, or waste removal to the affected area, apart from the very indirect effect of its benefits on the brain (which might be why some spinal injury patients do see minor improvement). For those unfortunate patients, partially differentiated neural stem cells, of the Neuralstem trial variety, must be directly injected into the CSF near the injury site to create the potential for benefit.

 

Thanks nonetheless for raising all these issues.

[John Schloendorn]

If your plan is to use GCSF mobilized CD34s for regenerative therapy, why not just take the GCSF, and then the cells are already in your blood.  Why bother taking them out and re-injecting them later? 

 

There are a variety of folks who used it in this way, and they do report neurogenesis / brain function.  I would guess that's most likely noise, but if it's not, it might be due to the GCSF also being a neurotrophic growth factor, acting on the neurons directly.  I don't find it plausible that it would have anything to do with the CD34 cells themselves, which are hematopoietic cells.  There might be something to your vascular story, but the actual levels of vascular engraftment you see just don't strike me as sufficient.  They're barely detectable with our finest instrumentation in animals, and who knows if that happens in humans at all.  Humans are higher fidelity creatures.  Our cells don't nearly slop around as much into other lineages as for example mouse cells do. 

 

 

 

 

[John Schloendorn]

As for the GCSF / leukemia risk,  I think that's all done in folks who were chock full of highly leukemogenic chemotherapy drugs already.  I'm not aware that this has been done in healthy GCSF-mobilized donors.  But if it has, I'd love to see it, please post a link.  (it's so hard to do selective searches for this stuff...)

[resveratrol_guy]

If your plan is to use GCSF mobilized CD34s for regenerative therapy, why not just take the GCSF, and then the cells are already in your blood.  Why bother taking them out and re-injecting them later? 

 

There are a variety of folks who used it in this way, and they do report neurogenesis / brain function.  I would guess that's most likely noise, but if it's not, it might be due to the GCSF also being a neurotrophic growth factor, acting on the neurons directly.  I don't find it plausible that it would have anything to do with the CD34 cells themselves, which are hematopoietic cells.  There might be something to your vascular story, but the actual levels of vascular engraftment you see just don't strike me as sufficient.  They're barely detectable with our finest instrumentation in animals, and who knows if that happens in humans at all.  Humans are higher fidelity creatures.  Our cells don't nearly slop around as much into other lineages as for example mouse cells do. 

 

Yes in theory there's no reason to extract CD34s then inject them back in. However there are some weird legal issues why that actually might be necessary, and it makes some sense, as a way of inspecting the level of population increase (and whether or not, in fact, I'm a Neupogen nonresponder). If I do this experiment as planned, then I'll report back all the details as to whether or not I reinjected.

 

As to GCSF risks, I can't find the original study which showed increases in leukemia risk. It's possible that, as you said, those studies have been focussed on reemergence or expansion of existing leukemia in patients taking GCSF to help support their immune systems during chemotherapy.

 

As to other serious risks: "A case was discussed in which a normal donor (a 54-year-old woman) developed a cerebrovascular accident 2 days after completing an uneventful stem cell donation [after taking GCSF]. She had no related symptoms or signs during the mobilization and collection procedure, and she never became thrombocytopenic during or after the collection. Another case was presented of a donor (a 64-year-old man) with a history of coronary artery disease who experienced a myocardial infarction after PBSC collection. In both instances, the relationship of the procedure to the event is uncertain. No other examples of vascular events have been reported, and the risk of thrombotic or bleeding complications has been quite low." The article mentions that GCSF is contraindicated in cerebrovascular patients because "In primates, an rhG-CSF–induced 15- to 28-fold increase in leukocyte count was found to be associated with cerebrovascular events related to neutrophilic infiltration of the brain parenchyma." Yet, I don't see any human cerebrovascular events apart from this one woman (granted, the study is from 1997). And it seems to me that, if one can deal with the short term risk, the long term prognosis of patients with cerebrovascular problems should be improved by GCSF.

 

Also note that there are other potential serious side effects, notably splenic hemmorage, so anyone considering this therapy needs to do their research. It's always a risk/reward analysis.

 

http://www.bloodjour...so-checked=true

 

But this goes right back to your point about extremely insufficient vascular engraftment. I think we're talking about two different scenarios here: CD34s love inflammation and vascular damage, but they couldn't care less about healthy endothelia. So if you inject them into a person with ideal vascular health, they probably won't do anything (unless as you mentioned GCSF is in fact a neurotrophic growth factor, which I have no reason to believe unless you have a study link). But if you inject them into someone who just had a stroke (especially a hemmoragic one), then I expect that they would congregate around the vascular damage in the brain, not just repairing existing damage, but adding new vessels in the process, just as they would if you cut your arm and wrecked some blood vessels. We're not even assuming a need to cross the BBB here.

 

My suspicion is that my cerebal endothelia aren't in the greatest of shape. If they were, then I would be very hard pressed to explain the stoke-like events of a year ago, and the headaches I had on and off for months afterward, vs. an MRI showing a nonspecific white matter hyperintensity but at this point, no evidence of tumor. Granted, I doubt my endothelia elsewhere are fabulous, either, so this therapy is broadly targetted, whether I like it or not. It's possible that my cerebrovascular damage, if in fact it existed in the past, has healed over to the point where CD34s would have no interest in fixing it (and hopefully overreacting by forming additional vasculature). There's no way to know for sure, so it's entirely possible that I come out of this "brain therapy" with a huge improvement in kidney or knee function, but no brain improvement. Just the same, if in fact this therapy will help my brain, then better now than when I'm much older.

 

I suppose all this is to say that I really need to think of this exercise more in terms of a midlife tuneup, and hope that the CD34s target the more serious problems preferentially.

Edited by resveratrol_guy, 21 September 2014 - 02:48 PM.

[John Schloendorn]

Well, if you want an honest opinion, it sounds like wishful thinking to me.  In adult humans CD34 cells are hematopoietic, not endothelial.  They "love" to be blood, and that is all.  There might be a separate, GCSF-mobilizable endothelial population in adult BM, which might be (if it exists) CD31 positive.  If you want to do an experiment with vascular potential, that's where I would look.

 

If you purify for CD34, you'd likely lose most of the CD31s.  (Are there rare CD34 / CD31 double positives?  Definitely maybe!  And what might their function be...?).  In any case, you'd still mobilize the CD31s to circulate into your blood.  So maybe no change to your protocol is needed.  If you do analytic flow cytometry, maybe just look at them, see what happens.  They might inform your vascular dreams more so than the hematopoietic progenitors. 

[resveratrol_guy]

Well, if you want an honest opinion, it sounds like wishful thinking to me.  In adult humans CD34 cells are hematopoietic, not endothelial.  They "love" to be blood, and that is all.  There might be a separate, GCSF-mobilizable endothelial population in adult BM, which might be (if it exists) CD31 positive.  If you want to do an experiment with vascular potential, that's where I would look.

 

If you purify for CD34, you'd likely lose most of the CD31s.  (Are there rare CD34 / CD31 double positives?  Definitely maybe!  And what might their function be...?).  In any case, you'd still mobilize the CD31s to circulate into your blood.  So maybe no change to your protocol is needed.  If you do analytic flow cytometry, maybe just look at them, see what happens.  They might inform your vascular dreams more so than the hematopoietic progenitors. 

 

So you really might be on to something here. Let me see if I can understand your theory properly.

 

On the one hand, we have the above Texas Heart Institute study, which says that human CD34+ cells can differentiate into endothelial cells as opposed to merely circulating blood cells: "The first attempt to use CD34+ cells for the treatment of a peripheral vascular disorder was described in the seminal report that first characterized the endothelial progenitor cell. Asahara and colleagues used a murine model of hind-limb ischemia (in that instance, via surgical resection of a segment of the femoral artery) to show that chemically labeled human CD34+ cells integrated into new capillaries that selectively formed only in the ischemic leg and not in the contralateral uninjured limb. The fate of a portion of the systemically injected cells was shown to be differentiation into endothelial lineage cells, documented by the co-localization of the label used to mark the injected CD34+ cell with other endothelial cell markers such as CD31 and UAE-lectin, indicating that the CD34+ cells had become fully differentiated endothelial cells. Although the report did not evaluate the functional benefit of the injected cells in terms of blood flow within the ischemic limb, the article did establish the groundwork highlighting the angiogenic potential of CD34+ cells." Indeed, this is the only mention in the entire article of CD31s.

 

So if your point is that CD31s are endothelial precursors much moreso than CD34s, then how do we explain the above study showing so many cases of vascular repair in the presence of CD34s? Is it:

 

1. As you suggested, there are bivalent CD31/34 cells which happened to be mobilized by a CD34 mobilizing agent, even though it's their CD31 receptor which is most responsible for their angiogenic effectiveness?

 

2. We don't need to mobilize CD31s from the bone marrow, because there are plenty of them in circulation under normal circumstances. But they don't put much effort into angiogenesis unless we spike the plasma with a huge CD34 population?

 

3. Both #1 and #2 are false. But mobilizing CD34s from the bone marrow has a knockon effect which mobilizes CD31s. So if in fact we had the CD31-equivalent of GCSF, then we would obtain equally good results without any CD34 mobilization. (This seems unlikely because it would imply that injecting the mice with CD34s somehow signals back to the bone marrow to release CD31s, but maybe.)

 

4. Something else.

 

Analytic flow cytometry is a good suggestion. I'm not sure that's available to me economically or logistically, but I will try.

[John Schloendorn]

Hmm no.  CD31 isn't "responsible" for angiogenesis.  It's just a marker.  Many non-endothelial, mature blood cells express CD31.  But the CD31+ population also seems to contain a lot of vascular potential.  GCSF mobilizes some CD31 cells, which is not surprising, because mature blood cells like neutrophils express CD31.  If I try to rephrase -- an interesting science question would be whether the GCSF-mobilized CD31+ population also contains vascular lineage cells, and I don't think we can definitively answer that in adult humans, but I don't know everything that's out there. 

I'm not necessarily suggesting a specific experiment at this time... Just want to put these things on your radar, so if something weird happens, you can try to make sense of it against the backdrop of those issues. 

 

So yes.  Your 1.2.3.4 are all excellent questions and I'm happy that you pen them down so eloquently.  I just don't have answers relevant to grown-up humans, and quite likely nobody does.  That's why I like your experiment.  It feels like it may well shed some light, but I can't say specifically how so

[resveratrol_guy]

Hmm no.  CD31 isn't "responsible" for angiogenesis.  It's just a marker.  Many non-endothelial, mature blood cells express CD31.  But the CD31+ population also seems to contain a lot of vascular potential.  GCSF mobilizes some CD31 cells, which is not surprising, because mature blood cells like neutrophils express CD31.  If I try to rephrase -- an interesting science question would be whether the GCSF-mobilized CD31+ population also contains vascular lineage cells, and I don't think we can definitively answer that in adult humans, but I don't know everything that's out there. 

I'm not necessarily suggesting a specific experiment at this time... Just want to put these things on your radar, so if something weird happens, you can try to make sense of it against the backdrop of those issues. 

 

So yes.  Your 1.2.3.4 are all excellent questions and I'm happy that you pen them down so eloquently.  I just don't have answers relevant to grown-up humans, and quite likely nobody does.  That's why I like your experiment.  It feels like it may well shed some light, but I can't say specifically how so

 

Anyhow, thanks for raising the CD31 issue. I had no idea about this. I actually delayed my final scheduling so I could read your reply. But I plan to nail down the date this week.

 

For the record:

 

I found your assertion that GCSF mobilizes CD31s quite surprising, because an Internet search revealed no clear evidence of that. But then I did some digging and found that maybe you're right, because c-Kit+ and Flk-1+ cells apparently have endothelial generation properties, and they somehow cause CD31 integration into new endothelia. This makes it looks like CD31s are doing the construction, but if that's true, then c-Kit and Flk-1 are the construction managers. It's possible that CD34s look like the heroes because they probably constitute a much higher percentage of the cells that GCSF mobilizes, but maybe it's these other cell types that are doing the real management. (Or maybe the CD34s are managing them.) http://atvb.ahajourn.../4/751.full.pdf

 

But then it turns out that GCSF decreases CD31 expression -- at least on cells which are also CD34+. "At day 3 to day 5 following the onset of G-CSF administration, a strong decrease of CD44 [sic] and CD31 expression was observed on mobilized CD34+ cells compared to controls" http://onlinelibrary...ls.18-4-281/pdf
 

[kaypeeoh]

This may be apples/oranges but I've had stem cell treatments for torn Achilles tendons.   I tore both during a 50 mile race.  One heel had successful  prolotherapy  treatment.  The other had it as well but it never healed so the next step was stem cells.  As the OP mentioned, marrow is extracted from the hip.  Then it was injected into the Achilles.   I had the treatment nine weeks ago.  It seems to be healing the tendon.  At its worst the insertion on the heel was larger than a chicken egg, not allowing me to wear shoes and too painful for walking, much less running.   The swelling is 90% gone in the insertion and I'm back to running.  

 

BTW, marrow extraction was horrifically painful.  Three nurses had to hold me down while marrow was being sucked out of my hip bone.  In comparison,  injecting the marrow into several spots along the heel/tendon was nothing even though for each injection the needle had to hit bone. 

 

kpo