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markkat

2,184 karma · joined May 21, 2010

Ann Arbor MI. Working on https://foreverlabs.com, https://hubski.com, and https://tincan.ninja.
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markkat··on Ask HN: Has anyone undergone stem cell treatment for auto-immune disease?
The trial you linked (as well as the two other registered trials using mesenchymal stem cells for Ankylosing Spondylitis that I found) are using allogeneic (donor) MSCs. I've been in MSC research/development for 17 years and now cryopreserve them as a service (Forever Labs YCS17). From my experience and knowledge of clinical efforts, allogeneic is limited by immuno-rejection of the MSCs after a few days. That's not to say that they can't provide benefit, but just that their window of action is limited as your body recognizes the donor cells as foreign, and weeds them out (perhaps in AS this is enough). The allogeneic issue is actually why I started banking them. I wanted my own young MSCs available to me later in life.

I'd be curious if you can get the clinic in China to expand your own MSCs. I did some MSC research in Beijing long ago. IMO they are ahead of us in many respects, but they also push the envelope more, and you need to be cautious. That goes for everywhere, actually. Just for different reasons.

markkat··on Ethereum Sharding FAQ
Ponzi schemes are terrible. Many ICOs aren't much more. However, blockchain enables digital scarcity. That's an interesting piece of technology right there. Using it as a state-machine is a very interesting application of it. IMHO many negative emotional responses come from scamming applications, many positive ones from new possibilities created by the technology, some of both are just due to the transformative nature of its application.
markkat··on Ethereum Sharding FAQ
TBH part of what makes me so bullish on Ethereum is how much of an emotional reaction it produces, both for and against the technology, all the while it continues to gain mindshare and utility.
markkat··on Ask HN: What Social Media are you using outside HN?
https://hubski.com thoughtful conversations
markkat··on The Worsening Cosmic Ray Situation
Hopefully it’s less than 1 day in length, so those on the far side of earth are shielded.
markkat··on Bitcoin mining and energy consumption
It's also not as decentralized as intended in the white paper in regards to transaction. First sentence in the abstract: "A purely peer-to-peer version of electronic cash would allow online payments to be sent directly from one party to another without going through a financial institution."

http://nakamotoinstitute.org/bitcoin/#selection-37.4-37.173

Most people trading BTC atm are not trading BTC, but trading ownership of BTC using a traditional database.

markkat··on Bitcoin Mining Now Consuming More Electricity Than Many Countries
Perhaps this solves the Fermi Paradox.
markkat··on Launch HN: Forever Labs (YC S17) – Stem-Cell Banking
We filed IP on a solution to this in June. :)
markkat··on Blockchains: How They Work and Why They’ll Change the World
I feel the same. I can't fathom the lack of imagination, and IMHO that's what it is. I've loaded Lemonade Stand on an audio cassette, and with the same fingers, I now type this on a black wafer on a plane.
markkat··on Launch HN: Forever Labs (YC S17) – Stem-Cell Banking
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.
markkat··on Launch HN: Forever Labs (YC S17) – Stem-Cell Banking
In most cases, you cannot. Cells that are not your own are cleared from the body or rejected in a short time.
markkat··on Launch HN: Forever Labs (YC S17) – Stem-Cell Banking
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.
markkat··on Launch HN: Forever Labs (YC S17) – Stem-Cell Banking
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.
markkat··on Launch HN: Forever Labs (YC S17) – Stem-Cell Banking
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.

markkat··on Launch HN: Forever Labs (YC S17) – Stem-Cell Banking
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.

markkat··on Launch HN: Forever Labs (YC S17) – Stem-Cell Banking
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.
markkat··on Launch HN: Forever Labs (YC S17) – Stem-Cell Banking
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.
markkat··on Launch HN: Forever Labs (YC S17) – Stem-Cell Banking
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...

markkat··on Launch HN: Forever Labs (YC S17) – Stem-Cell Banking
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.

markkat··on Launch HN: Forever Labs (YC S17) – Stem-Cell Banking
In some cases, that may be possible. We have not explored registry/donation at this time.
markkat··on Launch HN: Forever Labs (YC S17) – Stem-Cell Banking
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.
markkat··on Launch HN: Forever Labs (YC S17) – Stem-Cell Banking
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.

markkat··on Launch HN: Forever Labs (YC S17) – Stem-Cell Banking
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.

markkat··on Launch HN: Forever Labs (YC S17) – Stem-Cell Banking
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.
markkat··on Launch HN: Forever Labs (YC S17) – Stem-Cell Banking
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.
markkat··on Launch HN: Forever Labs (YC S17) – Stem-Cell Banking
I don't know about smoking, but there have been studies showing the positive impact of exercise on stem cell health.
markkat··on Launch HN: Forever Labs (YC S17) – Stem-Cell Banking
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.
markkat··on Launch HN: Forever Labs (YC S17) – Stem-Cell Banking
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.

markkat··on Launch HN: Forever Labs (YC S17) – Stem-Cell Banking
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.

markkat··on Launch HN: Forever Labs (YC S17) – Stem-Cell Banking
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.
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