Hi Mark, Would this be different from than "cord banking", which is offered to new parents? I don't mean in the technique, I mean in the type of cells retrieved and their potential long term benefit. I only ask because the American College of Obstetrics current position is not to store cord blood as a form of "biologic insurance" ( https://www.ncbi.nlm.nih.gov/pubmed/26595583 ) and was wondering what your thoughts on this are. It's a decision I, and some of my friends, have had to face as new parents.

As mentioned elsewhere here:

>>The cell populations are actually quite similar; there are both mesenchymal and hematopoietic stem cells in cord blood and bone marrow. In many ways, our service is 'cord blood banking for adults'. However, unlike a cord blood bank, we are developing potential rejuvenative therapies using these cells.

The use of cord blood stem cells has been dramatically low. I believe that around 1 in 14000 are used. That said, cord blood has long intended to be only used for rare blood cancers.

We see the landscape changing, using such cells for age-related disease, but also for rejuvenation. Given the low historical use, it's little wonder why storage isn't seen as high-priority. Personally, I see the young biology in cord blood as an asset that will grow in value. However, it should be noted that cord blood storage has been found to be of variable quality, it's worth going with a reputable service.

How old is too old to use my stem cells/ I'm 64 in 2 weeks.

The decline in functionality begins to be detectable between 20-40, and accelerates with age. This study has a number of measures regarding bone mesenchymal stem cells (which are included in what we collect and store):

https://www.ncbi.nlm.nih.gov/pubmed/18248663

Ideally, we all store at 18. However, my mother just stored at 70. Her mother lived to 93, and two of her aunts over 100. She decided that in 10 years, she might be glad she did. My own cells are 40. I am 42.

I'm sure it was free for your mother, because she is your mother, so why wouldn't she?

For the rest of us who have to pay, what are the realistic odds a 64-year-old will get any sort of benefit out of banking stem cells?

knowing markkat and his mum, she likely paid for the procedure.

Do factors like Smoking and Drinking influence the quality of the stem cells you can procure? For example, if one has been smoking heavily for 5 years, is it beneficial to "detox" and then have cells harvested? Is the quality of gathered cells different based on lifestyle, or do MSCs have impunity in this kind of situation?

I don't know about smoking, but there have been studies showing the positive impact of exercise on stem cell health.

I like it but there are some major questions:

1. What kind of stem cells do you get from bone marrow pluripotent?

2. Do we know how long samples last in cryo-preservation? Eg. is there any example of a 60 year old stem cell that was able to actually seed something biologically functional?

3. Is there a roadmap for some system that tells the user how and when they would request their cells to be used? Or is it just based on when their hypothetical doctor says they need to collect them?

4. Assuming you donate at 30 and live till 90, you are paying ~$17,000 to store these cells. What kind of likelihood do you see on getting $17,000 worth of value out of storing these. Asked another way:

If I was 90 and had a two stem cells in front of me at the stem cell market one that was free and was 90 years old and one that was 17,000 and was 30 years old, would the 30 year old one be worth the 17,000? Or do we know yet?

1. There may be few pluripotent cells in what we collect, but the majority of stem cells collected are multipotent (mesenchymal and hematopoietic lineages).

2. We haven't been cryopreserving stem cells for 60 years, so that is impossible to know. However, there is evidence that bone mesenchymal stem cells can be stored for more than 20 years: https://www.ncbi.nlm.nih.gov/pubmed/22280954 In my own experience, I have used cell lines that were stored more than 30 years, and primary cells stored more than a decade. Evidence suggests that the freezing and thawing process have the greatest impact, and that time in liquid nitrogen does not.

3. Once collected, you have a dashboard where you can log in and see/request your cells. We are working on rejuvenation therapies that employ these cells, so such a roadmap might develop should we have success.

4. I would not venture a guess.

In response to answer 2: how do you account for the risk of storage invalidating stem cells after 60 years, if you've only experienced useful 30 year-old cell lines? Put another way, why would I pay $7,000 if neither you nor I knew if my cells would still be useful to treat disease when I'm 80, assuming I stored them at 20? Do you have a method of propagation in intervals, ex. thaw, expand each set of cells every 10 years, and re-freeze? You mentioned in an above comment[0] that you'd need a clinical trial to have the legal ability, so perhaps not?

[0]: https://news.ycombinator.com/item?id=15386671

We aren't propagating at intervals currently. However, it's something that could be done; batch samples could be set aside for that purpose alone, also, one control sample could be divided and tested every 5 years. It's an interesting question: if I culture my cells after 20 years, then preserve them for 20 more, is the viability higher than 40 years of preservation alone?

Thanks for the question.

Thanks, great answers.

I thought extracting bone marrow was very painful. Can you comment on the procedure and pain involved?

A bone marrow biopsy is much more painful than an aspiration, which is what our physicians do. There is variability, but my own experience was a fleeting cramp (3 out of 10), that lasted about 15 seconds. I have been many of our collections, and that's typical. A local anesthetic is used, and mostly what you feel is pressure. You don't see anything, because the draw is on your lower back. Our physicians often prescribe an oral pain killer, and sometimes something to relax you. However, a surprising number of our clients decline both, typically because they want to drive home. The procedure takes about 15 minutes from laying down on your side, to standing up again. You are usually in and out within 1 hour.

I found it to be quite painful for about 10 minutes (the length of the aspiration procedure). Once the procedure is over, I would describe the sensation as "annoying, not particularly painful" for about 48 hours.

I've had an aspiration done. It was mostly just uncomfortable 3/10, with a few moments of pretty sharp pain more like a 6/10. However, those moments were brief and it was totally fine afterwards.

I also turned down some more potent painkillers beforehand, so if I had taken those instead of just the local anesthetic, it likely would have been less unpleasant.

Mild discomfort followed for a few days and within a week or so I had forgotten about it.

The speed of extraction helps determine the intensity. If it's very slow it's a mild sharp pain - difficult to describe otherwise. If it's extracted too quickly that mild sharpness becomes super intense. It's an interesting experience.

The discomfort is difficult to describe. I best describe it as a cramp. We believe that the negative pressure is in part to blame, and we have filed IP on a possible solution.

I believe that the negative pressure/vacuum is known to be the cause. One obvious solution would be to replace that pressure with a solution, probably your own plasma or similar - and then you'd just need to determine the best technology to apply for the system to allow for equilibrium..

We filed IP on a solution to this in June. :)

This is a neat startup idea.

Can you point me to research that this works? I saw some blog posts but I couldn't find any research articles.

Thanks! Here's a small collection of research:

https://foreverlabs.com/blogs/research

Also, here are some recent clinical trials using autologous bone marrow for treatment of heart disease or stroke:

https://clinicaltrials.gov/ct2/show/NCT01716481 https://clinicaltrials.gov/ct2/show/NCT02438306 https://clinicaltrials.gov/ct2/show/NCT01569178 https://clinicaltrials.gov/ct2/show/NCT01652209

Also, searching https://clinicaltrials.gov for 'autologous mesenchymal' will produce many results to peruse.

For the non-biologist: What's between this and an Umbilical cord blood bank?

The cell populations are actually quite similar; there are both mesenchymal and hematopoietic stem cells in cord blood and bone marrow. In many ways, our service is 'cord blood banking for adults'. However, unlike a cord blood bank, we are developing potential rejuvenative therapies using these cells.

What happens to my stem cells if you go out of business?

We currently have enough clients that the annual storage fees paid in more than cover the costs of our repository. We are actively pursuing two options to address this possibility: 1) The cell banking service is a separate entity, and all of us who have banked continue to pay into that entity keeping it funded, even if Forever Labs were to dissolve, and 2) An insurance policy covers long-term storage if Forever Labs dissolves.

All of our cells are banked, as are my wife's and family members. We are addressing this.

That said, your cells remain your own. At any time, we will ship them to another biorepository for $300.

What about redundancy? I'd like an option to bank at multiple locations.

I'd assume perhaps with different organizations as well, so if one organization becomes say unresponsive - then you have access to another source?

We've had a few clients ask about this. It's something that were will likely offer in the future. Our biorepository is currently in MA.

Let's say I put my stem cells in storage last month. What can I do now with banked stem cells if I needed them for some reason? Can I fix my knees from my banked wisdom tooth stem cells? Are the benefits all just hypothetical and in the future currently?

The benefits are not hypothetical, but are in the clinical trial phase. Numerous are phase 3, however. That said, this is not a 'save for next week' service. The idea is that your young biology will likely be advantageous, as the decline in your stem cell health is certain.

>Can I fix my knees from my banked wisdom tooth stem cells?

That might be possible, but isn't currently. Most trials for osteoarthritis use mesenchymal stem cells isolated from bone marrow or adipose tissue. It remains to be seen if the FDA approves cells by type or source-specific. Typically, all variables that can be controlled for are, so source-specific cells will probably be the initial requirement.

I noticed that you recommend 18 years old or older. How does this differ from a company like Cord Blood Registry[1] which evidently takes and stores cells from the umbilical cord?

Your lifetime plans are attractive and your company opens up the possibility of storing stem cells (and their blue-sky future healing promises) for children who missed out the first time.

A comparison could help others decide and migrate over once their kids are 18.

[1] https://en.m.wikipedia.org/wiki/Cord_Blood_Registry

As mentioned above:

>The cell populations are actually quite similar; there are both mesenchymal and hematopoietic stem cells in cord blood and bone marrow. In many ways, our service is 'cord blood banking for adults'. However, unlike a cord blood bank, we are developing potential rejuvenative therapies using these cells.

>A comparison could help others decide and migrate over once their kids are 18.

We have considered this possibility.

How does the amount you take compare to the total amount of stem cells I have in my body? Does the process have any negative effect on my short term and long term health?

We collect 60mL, less than 10% of what may be drawn in a bone marrow donation by this method, of which there are no known deleterious effects. Our physicians suggest you take it easy for a day or so, but aside from a tender spot, recovery is almost immediate.

Curious your thoughts on the rate of acceleration of:

- the technology required to utilize stem cells for therapies

vs

- the technology required to generate stem cells from somatic cells

To my mind those two technologies likely overlap significantly. I am curious where do you see the most likely divergence. Or, in other words, what particular new technologies would you like to see come to fruition that would enable banked stem cells to be put to immediate uses without the requirement for a full-blown arbitrary genetic manipulation suite.

That's an interesting question that is difficult to answer in brief. I believe I covered it a bit in a Google Talk I gave that was posted a couple of days ago:

https://www.youtube.com/watch?v=aSRqd1JfoaI

In short, I see storing your youthful multipotent biology giving you an early onramp on pluripotent stem cell induction, however I am not as optimistic as some. Biology is complex and there are blind spots to intervention. We still struggle with male-pattern baldness.

I can say that we are working on what I would like to see come to fruition. That is, take our younger cells, and rejuvenate the bone marrow niche, using our young bone marrow as bone marrow. In addition to that simple 'heterochronic transplantation', I intend to determine how we can improve upon it. Some realistic avenues are 1) removal of resident senescent cells and 2) rejuvenation of the cells ex vivo prior to reintroduction.

What happens to our stem cells if we die? Can we donate them to family that might match or others if we don't have any? ARe they re-usable by others or just us only?

Per our client agreement, they are disposed of unless an arrangement has been made. In some instances, your cells could be useful to someone else (such as an HLA match for bone marrow donation), however for tissue replacement, you are your own best donor due to immune rejection/clearing of allogenic donor cells.

What an amazing idea.

What sorts of research you doing internally? Anything on long-term storage? I assume you're at least collecting periodic data.

Congrats on your good work and execution!

Thanks!

We do perform QA on samples post-freeze process.

We are working on some uses of these cells for rejuvenation purposes. We will be sharing specifics on that in the coming months. Here are a couple of posts that I made about one experiment:

https://foreverlabs.com/blogs/news/health-maintenance-we-can... https://foreverlabs.com/blogs/news/donating-youth-to-yoursel...

What are the options for someone living in another country?

Currently, we only perform collections in the US. We do have clients from other countries that have banked with us. Our biorepository is in MA. Once you've banked with us, we can arrange to have your cells sent anywhere, however.

Can I have a real-world example or few use cases please?

Ok, I store my stem-cells with 37. And then? Can I stop aging forever or is it just for fighting diseases later?

One possibility is that you will have your young stem cells for the treatment of age-related disease later in life.

Stroke: https://clinicaltrials.gov/ct2/show/NCT01716481 Congestive heart failure: https://clinicaltrials.gov/ct2/show/NCT00644410

We are interested in using the cells to rejuvenate the decline in the bone marrow itself.

https://www.ncbi.nlm.nih.gov/pubmed/22355586

This is something that we are working on.

I believe I banked my stem cells when I got my wisdom teeth removed. Is this a different product than that? How so

There are mesenchymal stem cells (MSCs) in dental pulp. I have not studied them myself; however, they are reportedly similar to bone marrow MSCs. We bank all the nucleated cells in the bone marrow for two reasons: 1) there are high numbers of MSCs and hematopoietic stem cells (which build blood and immune cells), as well as endothelial progenitor cells (which build vasculature) and others such as marrow stromal cells, pericytes, etc, and 2) most trials employ bone marrow-derived MSCs. The significantly higher numbers are an advantage from an expansion standpoint, and the diversity of cells for applications. Still, having your young biology from your teeth (as long as the cryopreservation is done properly) is an asset, IMO.

Is this service necessary only because of US legal restrictions about growing stem cells in a lab?

I'd even be interested to know just your general take on US vs International regulations on stem cell research and if it affected how you built Foreverlabs.

Edward with FL here.

To answer your question, no. Because our stem cell niche degrades over time, we perceive a strong value of banking to come from the delta between when you banked, and when you employ your younger biology in future applications. The current regulatory environment doesn't change that calculus.

Also, we wouldn't want to expand/grow your sample before freezing anyway. The particulars of the expansion itself could change depending on the application, so we want to preserve them in a state that will afford the broadest range of future use.

Regarding the second half, I'll let Mark jump in when he comes back if he wishes. In the lab, he's had over a decade and half to muse about the regulatory environment. I can tell you that as we see it, we're near the cusp of where cellular therapies begin to transition from the clinic to the marketplace.

How much do you take? Do you think this is enough for any number of possible use cases in the future e.g. multiple diseases, experimental treatments, etc. Is there a real possibility of running out of banked stem cells?

We collect 60mL. There are normally about 10-15M nucleated cells recovered per mL of bone marrow. Stem cell counts are typically 0.01% of this (MSCs are about 1000/mL). We bank the cells in multiple chambers (3 larger ones, 5-6 smaller ones) so that you can draw them up multiple times. As they can be greatly expanded, it is our intent that the cells be grown to large numbers and then those portions cryopreserved. As an experiment, I have done this with my mesenchymal stem cells, and now have more outside of me than inside of me. If properly managed, a vast pool of cells could be created to draw upon. It's worth noting that we have gotten much better at expanding these cells over the last decade (decreasing negative effects of expansion). I expect that trend to continue.

Can you clarify what negative effects of expansion means? Thanks

If expanded over many passages in culture, the cells can degrade, much like they do due to age. For this reason, it is advantageous to start with sufficient numbers (thousands), rather than a few cells. However, as mentioned, we have improved culture conditions greatly in the last decade (ex. growing mesenchymal stem cells in a 3D matrix rather than flat on plates), which has extended our ability to generate more cells.

Very interesting! For the older crowd here, is cloning + stem cell extraction of the clone an option?

I'd love to be able to clone myself. I think the laws/technology aren't ready for that however.

Not something we provide! :)

Curious, instead of storing your own blood, can you somehow benefit from the stem cells of your children when they are 18? #askingforafriend

In most cases, you cannot. Cells that are not your own are cleared from the body or rejected in a short time.

Do you see any possibility for regrowing/regenerating degenerated spinal discs using stem cells in the near (5 to 10 years) future ?

Is it legal in the US to store stem cells? From my understanding it wasn't, at least not to allow them propagate?

It is legal to store them. If you want to expand (grow them to greater numbers) AND use them therapeutically, then you must be part of a clinical trial in the US. Many clinical trials using these cells expand them. I have grown some of my own, but have not used them to any purpose.

What's the rough one-time cost for storage, if anyone knows?

Also, what's the optimal age range to store these?

Cost can vary between markets, but it's generally around $2,500 for collection, plus $250/year for cryo-storage. If you don't want to pay for yearly storage, there is a lifetime storage plan for $7,000 which includes collection, and as the name suggests, lifetime storage as well.

Optimal age is addressed here: https://news.ycombinator.com/item?id=15386117

How is this better than using skin cells to create induced pluripotent cells?

Currently, iPS has a high risk of teratoma or malignancy. We haven't yet been able to induce pluripotency in a safe manner. I do believe that it is likely that one day we will overcome this obstacle, however having youthful multipotent cells will remain an advantage then. Age-damage to cells increases the risk of malignancy when inducing stemness.

Could I use this to donate stem cells to someone else later down the line?

In some cases, that may be possible. We have not explored registry/donation at this time.

this is very interesting, how long can our youthful stem cells keep alive ? Is it that possible youthful stem cells get old, too, or malfunctioned ?

Outside of the body in culture? They do seem to age if grown for very long periods of time. This is why we cryopreserve them, it essentially freezes them in time.