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Stem cells shown safe, beneficial for chronic stroke patients (stanford.edu)
254 points by kensai on June 3, 2016 | hide | past | favorite | 92 comments



Autologous mesenchymal stem cells are turning out to be one of the most underappreciated advancements in medicine today, and scandalously the FDA is slowing progress in the field by seeking to prevent doctors from harvesting and reintroducing one's own stem cells back into the body.

MSC's can be harvested from one's own adipose tissue with a little bit of liposuction.

The process of separating the stem cells from fat is called stromal vascular fraction.

It's an astoundingly easy process to do [1]. The equipment is inexpensive, and so far the procedure has been shown to be safe.

MSC's have been shown to improve COPD, and reduce the allergic response that triggers asthma. Skin damage healed, cartilage and joint injuries repaired, and even MS put in to remission,

MSC's administered via IV flock to areas of inflammation and damage and begin to repair it. The cells know what to do. Local administration is even better, as in this study or in cases of back pain and joint injuries.

Autologous treatments should not be considered biological drugs and subject to monopolization by biotech companies through decade long clinical trials and FDA approval.

These are our own cells from our own bodies. Doctors should be free to practice and innovate in this sphere, and in this case innovation is mostly just dosage, frequency and delivery method because the cells know what to do.

I believe that in the next decade or two, autologous stem cell treatments will be basic preventative care for everyone, a treatment each year will repair damage before it becomes pathology.

[1] https://www.miltenyibiotec.com/~/media/Files/Navigation/Rese...


I've been working with MSCs for more than 15 years, mostly in stroke, and I agree completely. It's worth noting that this trial used donor cells, and that might be part of the reason they don't remain after a couple of months. There is evidence that autologous cells persist longer, likely because they aren't swept up by immune rejection.

What we and others have found is that age of the donor inversely correlates to their therapeutic potential. For that reason, I founded Forever Labs, Inc. http://www.foreverlabs.co/

We bank young MSCs so that they can be preserved for therapy later in life. I banked my own two months ago.

We prefer bone marrow MSCs as the BM also contains blood progenitor and stem cells, whereas adipose tissue does not.

*We are fast expanding and raising; email in bio. ;)


If you banked your cells today at the age of 30, how much therapy can be hypothetically produced from that in the future?

Is it a store that depletes as you use it? Or can banked stem cells be replicated to create more reserves?


Different therapies will likely require different numbers of cells, and most clinical trials using MSCs involve preliminary expansion of the cells. We store multiple aliquots of your cells so that only a portion may be thawed at a time.

We don't expand the cells at this time, but will likely offer expansion services in the future.

Yes, by expanding you could create a very large reserve of cells.


Hm, this will make me sounds like a smart-ass, but ever since I learned about stem cells I was wondering why one does what you do. I mean, in some fundamental way it's kind of obvious. If your cells get damaged with age, why not store young cells and reintroduce them later? I realize that this isn't nearly as simple as I described, but the fundamental concept intuitively makes sense.

I'm glad to hear about your company. And I'd kind of proud that my intuition proved correct, even though I don't know much about the field.


Great minds think alike. ;)


Can people from other countries use your service (by traveling to one of your locations?)

At what (maximum) age would the max potential benefit be achieved from harvesting? (ie, I assume it doesn't make sense for an infant to have this procedure, but assuming it's available throughout one's life, when would be the optimal time to do it?)


>Can people from other countries use your service (by traveling to one of your locations?)

Yes.

>At what (maximum) age would the max potential benefit be achieved from harvesting?

Functional data of cells harvested from donors of different ages shows much variability between individuals, but after about 40, a slow trend in decreased differentiation potential, proliferation, and other measures, appears. The decline depends upon the measure, but in general, suggests 20-40yo is the best window, and closer to 20 is likely better. The functional decline continues, but seems to get steeper around 60. Between 70-80, some studies report that the numbers of stem cells start to drop in addition to function. Here is a representative study: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2398731/


I think you just landed yourself a customer :)

MSC benefits are fantastic at replacing lost or damaged cells, however they are not bio-rejuvenation in the sense of turning back the clock with younger cells, unless one were to bank one's own younger cells?

If that is true, it would be, in a sense, an early SENS hack.

Very interesting. Will contact.


Sounds great! :)

There has been some animal work that suggests transplantation may have that effect:

http://www.ncbi.nlm.nih.gov/pubmed/23967009 http://www.ncbi.nlm.nih.gov/pubmed/25707248

There is much research to be done, but the technology to transplant young bone marrow stem cells to one's older self exists today.

To be honest, that is part of my personal motivation. 'Autologous stem cell time travel' is low hanging fruit. We preserve the cells in multiple aliquots with the assumption that they might be used for multiple purposes, including expansion.


Couple questions:

- you're using bone marrow stem cells and using the same confusing acronym as mesenchymal stem cells. As someone who has been out of active research for several years, what is the difference? And are there other acronyms that are accepted?

- BM stem cells through bone marrow harvest used to be the order of the day for repopulating immune systems following irradiation of marrow for some leukemias. Nowadays the state of the art is that those stem cells can be harvested by fractioning whole blood, so you only have the hassle of a blood donation, rather than the serious and not to be sneezed at act of penetrating cortex to harvest marrow. Is there any reason you can't get this from whole blood?

Thanks


People often use 'marrow stromal cells' or 'mesenchymal stem cells' interchangeably as scientific terms (but of course, there is debate) that refer to adherent colony-forming multipotent cells. We use 'bone marrow stem cells' as a non-scientific term that includes MSCs as well as hematopoietic stem cells and endothelial stem cells.

>Is there any reason you can't get this from whole blood?

The blood harvest process uses a machine, takes a few hours, and requires the prior administration of a protein that stimulates stem cell proliferation and release into the blood. It is preferable for some procedures, but for those reasons, not for ours.


Doesn't bone marrow harvest require a general and tapping into the ilium? I would rather sit attached to a machine for a few hours.


No, just a local. I described the experience here: https://news.ycombinator.com/item?id=11832220

It's not bad at all.


Out of curiosity, what is the procedure for obtaining the stem cells? Can it be done locally, would there need to be travel to one of your locations?


We are based in Ann Arbor, MI. We are currently opening operations in the Piedmont of NC, and CA (SF) will follow soon after. More cities after that.

If you are interested, contact us, and let us know where you are at.

The procedure is done with a local anesthetic. The entire procedure takes about 15 minutes from lying down to standing up. It is drawn from the upper part of your pelvis bone on your lower back. The most discomfort is a muscle cramp-like feeling that lasts about 5 seconds upon the draw itself. Personally, I rated it a 3.5 out of 10, as did my wife. Consensus is 3-4. Our CEO is a self-professed wimp, and he said it was a 4. :) I'd much prefer it to a cavity being filled. There is no recovery, just a bruise-like tenderness at that exact spot for a few days. I walked across town for lunch afterwards.


Wow, that is amazing. This is a random question but do you happen to know the study the data on this graph comes from? Fascinating stuff!

http://www.foreverlabs.co/uploads/4/9/3/9/4939113/5557005_or...


I believe it is adapted from this study: http://www.ncbi.nlm.nih.gov/pubmed/16041622 Thanks. I'll confirm and add an attribution, which should be there.


Is there a cancer risk associated with 'rogue' stem cells that aren't cleared from the body?


As mentioned in the article, transplanted MSCs have not been found to carry risk of tumor formation, and this is seen as one of their advantages.

Induced stem cells (IPS), or stem cells that are genetically modified may carry these risks, as there is overlap in the signaling mechanisms that maintain the undifferentiated state of stem cells, and that of tumor. In fact, stem cells naturally express more tumor-suppressing proteins as they age, which is thought to be a mechanism to prevent tumorigenesis resulting from damage accrued in the cells over time.


Cool! What is the cost for this procedure? I couldn't find this information on your site.


In MI/NC it is $3500 and $250/yr storage. Storage will remain constant, but there may be some market differences for the procedure.


That's totally more reasonable than I had assumed. Thanks!


Not sure if it's me, but your insightly* form seems to have a broken validation rule.

After I sign up for an information session, it says last name is mandatory even though I clearly filled it out.

FYI.


> and scandalously the FDA is slowing progress in the field by seeking to prevent doctors from harvesting and reintroducing one's own stem cells back into the body.

According to this article, what you're referring to is just the FDA putting stem cells under the same regulatory burden as most drugs.

https://www.statnews.com/2016/02/08/fda-crackdown-stem-cell-...

They have escaped this previously because the stem cells came from the patient, and not much was done to the cells before re-injection, so it's closer to plastic surgery.

I happen to think that that FDA is probably way too conservative (both on stem cells and drugs) and seriously inhibits progress, but I think it's misleading to suggest that they are slowing progress in a way specific to stem cells. The FDA has always had a mission to not just protect patients from harm, but also from being fleeced by useless sham therapies.


In this case the therapy is not useless or a sham, and it is autologous which has traditionally been an exempt area in this respect.

That the FDA has overturned its own history and precedent is the scandal, imho.

A benefit has been shown, to what degree and in which circumstances is being ironed out.

There is some hope, the FDA has liberalized to some degree in recent years and biotech has been a top performing sector. We live in miraculous times.


The FDA is cautious in this area because historically a number of stem cell injection therapies have led to tumor formations in the CNS.

That said they were not autologous mesenchymal stem cells. This study gives hope.

Refs: http://www.nature.com/stemcells/2009/0902/090226/full/stemce...

http://journals.plos.org/plosmedicine/article?id=10.1371/jou...

Old review from early 2000s http://onlinelibrary.wiley.com/doi/10.1002/ana.60000/full


I don't think you disputed my point.

> In this case the therapy is not useless or a sham

More precisely, in this case you believe there is enough evidence that the therapy is effective, but the FDA does not yet agree that has been established. Then, in congruence with its policy on unproven medical procedures, the FDA has severely constrained stem cell procedures.

> and it is autologous which has traditionally been an exempt area in this respect.

It's clear that there was little/no enforcement in this area previously, but now they have announced clarification that it is to be enforced. You may call that a change in the regulatory environment, but it doesn't appear to be a change in general policy.

The situation is very similar to 23andMe. 23andMe was flying under the radar and, when the FDA cracked down on them, they experienced a changed in their effective regulatory environment, but this is not reasonably interpreted as the FDA changing its tune (or overturning history or precedent or whatever).

Again, I wish the FDA allowed more of these things to proceed (including 23andMe and stem cells) but I don't think this is change.


The FDA has a lot of blood on its hands. Everyone, especially a chronically ill person on their deathbed, should be free to choose whatever experimental medical procedure they want. Not only is this a recognition of self-ownership, but it would provide invaluable medical research and could accelerate getting effective treatments to the ill.


So every con artist should be unrestricted in selling false hope to the most desperate of us?


Do you realize that this a straw man argument?


Do you realize that this is how the anti-vaxxer community gets along? And all the esotheric guys?


I don't, because I'm not part of those groups, and don't know anything about them, really.

But I can imagine that attempted smears-by-association (as you you are positing above) are common currency, in those communities.


I don't realize that because it's not.


When the original commenters said "Everyone, especially a chronically ill person on their deathbed, should be free to choose whatever experimental medical procedure they want", it's safe to assume he meant "within reason".

The "within reason" part is very important: As in, someone on their deathbed might have to go through certain hoops to get not-yet-approved treatment X (like signing waivers saying they understand the risks, etc); and there might other minimalist safeguards in place (such as that the chemicals are manufactured at regulated facilities; that the persons involved in administering the treatment have no criminal records or major fraud convictions against them) -- but ultimately, they can get access to treatment X.

By tweaking this to an extreme absolutist position -- "there should be no regulation of end-of-life treatments, of any kind, whatsoever; even if the person offering the trade is a convicted criminal and/ con-artist" you are standing up a false argument that the original commenter wasn't making.


It wasn't a strawman, but it was a pretty aggressive argument in bad faith.


You've never worked in a specialist medical clinic.

Edit: not intended to sound ad hominem


a) How do you know?

b) The phrase you're looking for is "argument from authority," which it is.


a) I don't know, it was a guess from experience.

b) Sometimes people cry 'ad hominem' after any statement that refers to the debating party ('you') and I wanted to avoid that.


thank you! fda is a leading cause of death in US in my opinion; from killing off inovation that would prevent death.

I worked at a medical startup that was bought by JNJ, it was high end surgery technolgy.

We made the first gen of our product, and it took 14 months to clear fda. Even though we made lots of improvments to the devices after, we never released them; that would have caused another horible fda clearance process.


There are excellent reasons why this is not the case:

http://harpers.org/archive/2016/06/hashtag-prescription/


Which is? (For those who don't want to sift through a nine page article)


I'm similarly lazy, but hopefully this paragraph captures some of the ideas:

> Caplan suggested that giving Josh the drug through the compassionate-use protocol might endanger its approval by the FDA. In the worst case, Josh would die after taking brincidofovir, and that outcome would “be held against the drug and the company until they can show the drug did not kill him.” In the meantime, other patients would find their access to the drug severely restricted. What’s more, an online campaign powered by photographs of a sick little boy raised hard questions about fairness. “Those who are not very cute get less attention in their pursuit of unproven drugs,” Caplan wrote. “If Josh had parents who did not understand how to use social media, he would already be out of luck.”


Interesting, but does that not highlight even more so the backwardness of the FDA? If they are willing to take some anecdotal case where someone died who happened to be taking a drug--blaming it on the drug company, despite the clinical research which had been done, further delaying their going to market--that doesn't sound like a compelling argument for the efficacy of the FDA in these cases.


> MSC's have been shown to improve COPD

My grandfather died of COPD, and likely so will my Dad. He has COPD. And was diagnosed in his 50s. I am fearful of it myself, but thankfully unlike both of them I've never smoked.

It is a shot in the dark, but do you know anything off hand of having him participate in something like this in the US?


There are clinics and doctors that have been performing the procedure, lowest cost I have seen is $7k for a treatment. They can harvest, isolate and deliver his own MSC via IV and perhaps nebulizer.

It seems like the doctors that have been performing are silos of information right now. There is not a lot published on the web of their experience as practicing doctors, some of the best on the ground info I have found is from interviews of doctors practicing.

There are also very many published MSC trials showing a benefit.

It is a terrible thing to not be able to breathe well. I hope that this can help.


Thanks! I will try my best to look into this and hope he is willing. He doesn't talk about it much.


Wouldn't there be the concern that the cells would regulate themselves differently when introduced into a new environment?


The procedure has been done tens of thousands of times all over the world, so far it's been incredibly safe.


Are there other countries that are starting to specialize in this? Do you think we might see a black market form in the us?


There are still clinics in the US that will perform this procedure, despite FDA pressure. I am not an expert in the specifics of why or how, but I do know that this is reducing the number of doctors treating patients with MSCs and increasing the cost.

I don't want to travel to Mexico or Thailand or even Europe to have this simple procedure, and I don't want to wait 10 or 15 years and then have to pay monopolist, proprietary pricing for what would be an inferior technique compared to what a free, open source medical science would inevitably produce.


There are companies in the US that will set you up in Mexico or the Cayman islands where the regulations are more favorable (in that they do not exist). It's pretty exciting. FDA is lagging, but it's hard to blame them for caution given all the troubles they've experienced since the 90s.


Not autologous in this case.

http://www.san-bio.com/product/

The brain is immune privileged, so there is more leeway to use donor cells if that is the destination. Which isn't the case in most uses of stem cell transplants, as you point out.


Actually, the brain is not as immune privileged as was long thought. Only last year, lymphatic vessels were identified in the brain.

https://www.nih.gov/news-events/nih-research-matters/lymphat...


If the cells are already in your body what's the point of extracting them just to reinject them back in?


The cells are not injected into the same part of the body that they were extracted from.


The FDA is protecting people against sham treatments. The whole reinjecting things that come from your body canard has been around awhile -- look at PRP treatments for example. No compelling evidence exists that it actually works, but tons of clinics offer it because Tiger Woods got it once. There is a legitimate danger with stem cells that you could introduce cancer (this has happened in some studies).


I suspect that the processes to produce these will get patented if not the results, but it's still encouraging that new treatments can be made by using cells from our own bodies.


Incredible post, thank you so much for a clear and concise overview.


What about androgenic alopecia? Is there potential there?


The study seems focused on just motor skill improvements. Was there work done to see if it helped with aphasia? Could this help aphasia?


It makes no sense to me that this is marked dead. Seems like a totally reasonable question.


The primary difference between this and most of the stem cell therapies delivering mesechymal stem cells - which are more or less the standard type of cell to use for the moment, the most studied and most characterized, no-one got fired for using mesenchymal stem cells, etc - such as those widely available via medical tourism is the delivery to the brain. That isn't something clinics do, for all the obvious reasons.

So I'm inclined to think that this is one of a number of different studies in recent years to demonstrate that the delivery methodology makes just as much of a difference as the type of cell lineage and any tinkering done to that cell lineage.


They've been doing this kind of thing over in China for some time now[1]. Science with a capital 'S' doesn't happen until the U.S does it though, and until that point and time all procedures are considered risky and dangerous. Even if you're going to die before any of it gets approved, you better not do any of this stuff.

[1] https://www.reddit.com/r/IAmA/comments/fu2ub/as_requested_i_...


Many people are aware that soon after President Obama took office, he authorized federal funding of embryonic stem cell research, which President Bush had resisted. The Obama administration made a big deal out of it at the time:

https://www.whitehouse.gov/the-press-office/removing-barrier...

What got swept under the rug was that at the same time, President Obama specifically rescinded a previous executive order that directed the HHS to "conduct and support" research using adult stem cells:

https://www.cellmedicine.com/obama-executive-order/

I don't think the Obama administration ever spelled out why, at the same time it was promoting ESCR, it decided to also deprioritize adult stem cell research, but I think this latest news -- along with all of the other advances of the past eight years -- has shown that moral issues aside, adult stem cell research is paying high dividends.


> I don't think the Obama administration ever spelled out why, at the same time it was promoting ESCR, it decided to also deprioritize adult stem cell research

It was all part of the same EO, which was accompanied on the same day by a Presidential Memorandum on scientific integrity in government decisionmaking on science and technology, and the rationale for the set of policy changes was explicitly to move toward allowing decisions on what avenues of science to pursue (not the goals, but the routes to the goals) to be guided by science rather than politics.

It wasn't deprioritizing adult stem cell research, it was letting the relative priority of adult stem research be set, and adjusted, over time based on science, rather than being set by political directive.


I read they don't turn into new neurons but rather release chemicals that stimulate growth and repair. Am I understanding correctly?


yeah, they say that the stem cells actually disappear after about a month but improvement continues well afterward. and they say its because of growth factors released by these cells.


Is it possible that the procedure itself, the act of drilling and poking needles into the brain, stimulated the improvement? The stem cells didn't linger and they're precursors to skeletal muscular cells so maybe they actually had no effect on the outcome? Is it possible/ethical to do studies where they drill and poke into the brain without injecting stem cells?


The article mentions they're now getting ready for a larger double blind trial. This one was I think a test for safety.


>It was designed primarily to test the procedure’s safety


I wonder why only 7 out of the 18 patients showed improvement? What could that mean?


You should compare that 7/18 with what happened to other 18 in the same condition. 1 year after stroke, it is quite safe to say that 0/18 would have any improvement in 1 month (the patients were testes also 1 month after).


Doc here. Not negative on this story, but it is completely false to say 0/18 would have improvement with standard care. Patients frequently improve from strokes; some quite rapidly. Maybe you had a typo?

The next step is intervention versus placebo. Strokes are very common. It should be easy to find patients to enroll.

Hopefully this will turn out to work and be worth the cost.


1 year after the stroke, the difference in a month is very limited in my experience. I am not a doc, but I've crunched some numbers related to this topic, what was your experience?


"Significant improvement" is 10 points on a 0-100 scale. Maybe others had what to their family would be significant improvement, but it didn't quite exceed the marker.

With one intervention using donor cells in 12 months, for stroke patients, that could be a big deal.. with improvement to the procedure or combining with other treatments maybe more could be achieved.


it could mean a lot of things, but at the very least it means 7 out of 18 improved.


What I found to be worrying is that the researchers seems to be unclear about how MSC is causing the improvements.

Also the improvements continues after the stem cells have disappeared. This seems to suggest the effect doesn't come from the MSC, but rather the chemicals the cell produces. Does that mean if we can synthesis the chemicals, we don't need the cell?


I hope the next trial works too, this is amazing. I wonder if this technique would work for other brain disorders like Alzheimer's?


Where's the link to the study?


Well, it looks like we can advance science without pretending killing human beings is ok, after all.


This comment and others you've posted break the HN guidelines. Please (re-)read them, and post civilly and substantively (or not at all) from now on.

https://news.ycombinator.com/newsguidelines.html

https://news.ycombinator.com/newswelcome.html


Please specify which ones and exactly how.


HN's rules don't work that way, partly because formalizing them would merely turn them into a long list with an infinite number of loopholes to be exploited, and partly because we'd die of boredom if we tried.

Users here are simply expected to live by the spirit of the law—civility and substantiveness—when commenting here. Snarky one-liners that characterize a (vague) opposing view as "killing human beings" fail the "civil and substantive" test. Plus there's outright rudeness in comments such as https://news.ycombinator.com/item?id=11663455 and https://news.ycombinator.com/item?id=11651181, which has no place here.


I always substantiate any of my one-liners. In this particular case see https://news.ycombinator.com/item?id=11836930 . Few things are more deserving of "snarky" treatment.

The other two (chronologically disordered) examples are a product of my indignation with an obstinate person who wasted people's time and, brazenly ignoring their arguments as well as my own, continued arguing FUD.

Bottom point: I am not malicious and I contribute. So I'd appreciate if the trigger was not pulled on me even though it's probably the only way to get one's comments removed from here :-/


Rules lawyering with the moderator isn't likely to work that well.


They have a pretty short comment history and no (visible) prior warnings (I was curious, so I looked). From the outside, the request is not unreasonable given the statement about "[t]his comment and others you've posted".


No one was ever performing abortions to obtain stem cells.


What I referred to is the death of a human early in its development (blastocyst) resulting from the steps necessary to derive embryonic stem cells (as opposed to those necessary for adult stem cell derivation like here and elsewhere)


You mean the leftover blastocysts that are otherwise disposed as medical waste after IVF treatments? I think I'd prefer they use them for medical treatments instead of fuel for an incinerator.


blastocysts aren't human beings so your post makes no sense.


As I understand, the blastocyst is a state of a human being in the early stage of its development, having in turn developed from the morula, and the zygote (the first cell).

If you want to argue semantics of the words or the phrase, we can do that. If you want me to use a dictionary to justify my use of the words "human" and/or "being", I'll do that. If you want textbook (medical) definitions, you can have it right away at https://goo.gl/ZFDcbg. And if you'd like more scientific literature backing, consult https://goo.gl/zXpbAu. If you are willing to cede that the nomenclature fits, but would like to now rank human beings by worth in relation to stage of development, I would like to provide arguments for why you shouldn't do that. Finally, if you have reconsidered everything, I would invite you to the Way, the Truth and the Life, as scary as that might sound. Peace be with you and yours.




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