Age-Reversing Stem Cell Treatment Succeeds in Human Trial | Dr Koji Tanabe

[00:02] that's very interesting because the why people get the pain in the knees and the people get the pain in the knees and the the the cartridge cells cartridge uh in the in the knee junctions is getting worse and then short smaller and smaller

[00:17] by the aging and that they are losing right and that's why they got the ache into knee junctions but once we inject these IPSF we can clearly see the rejuvenation of the cartridge they start to secrete more heal onic acid uh they

[00:34] they get lo they we succeeded to remove these pain pain from these knee these pain pain from these knee junctions or we can see the recovery

[00:49] pioneering stem cell scientist who co-authored the historic 2007 paper establishing human induced pluropotent stem cells IPSC's under the noble laurate shin uh Dr. Shiny Yamanaka and is now the founder and CEO of IPS in

[01:05] incorporated. So Dr. Tanab, welcome to modern health span. >> Thank you for inviting me and giving me this great opportunities to and explain the IPSC technologies. >> Thank you. So it is I the IPSC's are so

[01:21] exciting but I don't think they are perhaps as well understood and it's great to be able to talk to somebody who is working with Dr. to Yamanaka uh right when you know the the IPS-C's were first developed. So you were you were the

[01:37] co-author of the original paper with uh Dr. Dr. >> So when we look at IPSC's how what is the process like for creating them? because I think you know often we just

[01:51] say oh you know you you apply the yammonaka factors and the you get yammonaka factors and the you get IPS-C's but it's not that simple so can you talk about how the uh how the yammon factors actually create the IPS-C's

[02:06] >> yeah yeah let me introduce a little bit about the IPSC technologies right because uh our body is made it from the I think a lot of I think cells right but that's originated from the single fatilized deck Right that's coming from

[02:21] only single cells. So at the IPSC technology we can deprogram that these our body cells to the that younger state or fatized X state. So IPSC is the name

[02:34] is IPSC but that that's I think age debted stem cells right people using recently used a stem cells that's a 60 years old stem cells is a 60 years old stem cells but IPSC technologies can

[02:48] reprogram your body cell to age zero cells that's a technologies and how to do that and we identify the and how to do that and we identify the four important genes uh to reprogram um

[03:02] that these body cells to original at the fertyic state. >> Okay. And so the actual process I mean how reliable is the process? So we you

[03:14] know you say you know we you identified these four proteins and you you so you put the proteins on the cell and how how reliable is that? I mean what percentage seeds? >> Yes. Because the we have a various type

[03:30] of the various kind of cells right for example muscles for example like a eyes for example like a hairs right that each cells has a different combination the

[03:42] different combination of the genes right and here has a hairs combination heart has a heart combinations we when we inject these four factors so first I

[03:54] think misunderstanding or forget about I I'm I'm a skins. They forget about the I'm a blood. For example, we inject the yamaka for factor into the blood. They start to forget about they are they are blood first. they forget about the blood

[04:10] and then then I think the program then they start to believe they are f like a IPSC like a fatty that's a happening during the IPSC programming with that during the IPSC programming with that four factors uh that that's a mechanism

[04:24] what happening but the process is we are just only taking out the 30 mil blood just only taking out the 30 mil blood and we are isolating these original cell monoc monuclear cells from the your blood and we inject these Yamanaka

[04:39] factors inject into the cells the Yamanaka factors and then wait around the one to two months we can get the the one to two months we can get the IPSC they program uh changed uh from the

[04:52] IPSC they program uh changed uh from the blood to the IPSC's does it matter what the starting cell type is and if you start with a cell type that's closer so if you start with a stem cell like a mezenyan stem cell

[05:06] does it take less Is that better? >> Yes. So some science uh in the around 2007 2008 and people discussing about if we can start the reprogram from stem cell it's more e that's more easy but

[05:22] latest technologies I think we succeeded to increase the reprogramming efficiency doesn't matter we any type of the somatic cell we can efficiently somatic cell we can efficiently reprogram uh from any type of body cells

[05:35] but that's a really interesting question >> now in the reprogramming Right. We don't actually we we want to get all the way back to ipcs uh IPCS's right. Um but do

[05:47] back to ipcs uh IPCS's right. Um but do all the cells make it back and uh do if what happens to the ones that are not completely reprogrammed? So that's a problem right because I think they people call a partial

[06:00] reprogramming when we make up technologies I think some cells is transformed not become IPSC's completely but some cell is become IPSC's right but

[06:12] in vitrial reprogramming we can only picking up the free program cells from the partial program cells we can select the partial free program cells to use the vision medicine and the longevities is but however right because the if we

[06:31] cannot select these freed program cells and if we injected these partial in the bodies people I think probably highly have a high risk get the tumor risk or

[06:43] cancer risk >> that's why quality control and selection >> that's why quality control and selection is very important in this technology yes >> yes and so we we'll definitely get into that uh a bit later. So we we we have

[06:58] the IPS uh we have the cells they're sitting in a dish and then we we put the the amalaka factors these these four proteins into them. proteins into them. Do the cells get younger first and then

[07:14] they become stem cells or is it just all one process and do you know is there like a sta there stages to the reprogramming? >> Yeah. So let me introduce a little bit other like natural phen phenomenon right

[07:29] because I'm I'm adding a reprogramming scientist I'm really interesting human reprogramming but my starting point is not human reprogramming because you know right n can regenerate that they are lost of the limbs or or the tails or

[07:46] eyes even hearts right when they cut the eyes even hearts right when they cut the limbs that part can deprogram to the stem cells which which can become any type of body cells that's happening

[08:00] right in the in the natural phenomenons that we try to recapture well we try to that we try to recapture well we try to make a similar um phenomenance in the humans that that's happening in the humans and what's

[08:14] happening in the humans and what's happening as you mentioned first they are I think first I think they are forget about their original I think original uh features and first with the four factor injections and then start

[08:29] four factor injections and then start the rejuvenation and and also uh the rejuvenation and and also uh reprogramming for example like u to do I don't know whether you know it telomere is a one of the uh parts in the

[08:41] chromosome over the age that's getting shortened uh shortened but during the IPSC programming that's completely uh programming that's completely uh completely they expand I think with the

[08:54] A0 state that's happening during the IPSD programming and also during the over aging in our bodies we have a lot of uh modification into the DNA that's a like a dust I think DNA is modified and that's a cost of the aging but during

[09:11] the IPSC deprogramming that's a completely cleanup that during the this one to two months that's why people call the IPSC deprogramming process is a the IPSC deprogramming process is a rejuvenation process do uh because they

[09:24] try to go back your fertilized state that's everything the aging signal is also uh wiping up cleaning clean up during the IPSCD programming >> so can I just check my understanding so for new so I mean axelottals in

[09:41] particular I think that they regrow the limb so the cells that are close to the the injury they turn they do this pro reprogramming and they become they go that what happens? >> Yes, they I think if you cut the limbs

[09:56] that the limbs is a limb, right? Because they are skin or muscles or like that, right? But first they for they become a stem cells. They reprogram the stem stem cells. They reprogram the stem cells in the cut the injury site then

[10:10] they make they make the these various type of the tissues that's happening. That's my starting point. I want to do that the these things in humans. >> Okay. Okay, that's okay. That's really interesting. Okay, so [snorts]

[10:26] that that's kind of like the basics of how you go about creating these IPCS's, >> right? But as we talked about, you know, it's not it's the number of cells that get

[10:40] reprogrammed is not that many and and you need to be you need to do quality control because you you need to look at them and and not all of the cells end up them and and not all of the cells end up in the state that you want them. I mean

[10:53] a question in there. I mean if I take a 100 cells and I apply the Yamanaka factors what percentage will be come out as clean IPCS's yes the answer is very high efficiency at this time moment by our technologies

[11:10] at this time moment by our technologies allowed I think 80% or 90% almost all allowed I think 80% or 90% almost all cell become IPSC's with our technologies but I think 20 years ago [laughter] that's I think a percent is only 1% or

[11:23] 2% less le than 1% or 2% uh that's a percentage but at least in latest technologies another slide more more static more than 80% become IBSC

[11:35] >> okay so let's talk about the changes that have happened and and so what is it that you are doing that changed this from like 1% to 80% what what are the key things that you need to do to ensure uh the correct outcomes

[11:52] uh the correct outcomes >> so that in First I think a cell should forget about their original features right for that I think we are uh we try to inject these a lot of genes but the balance and also amount of the these

[12:09] genes expression is really important right because if we because four factors right one factor is I think more I think too much expression in the cells uh existing in the cells that's I think the cell is going to the completely

[12:23] cell is going to the completely different directions but this balance or timing is really important to uh realize these highly program high the the program with high efficiency >> you're reprogramming like Xvivo right so

[12:37] you take cells actually what kind of cells do you start from at IPS >> so we are starting to make we are using the blood cells to make IPSCS

[12:52] Because of course we can make IPSC from the skins of course from the hairs from hair follicle cells and also I think some the cells in the urine too but we

[13:05] some the cells in the urine too but we try to make a clinical grade IPSC's try to make a clinical grade IPSC's right uh in that case sterity is very important without I think a virus or bacteria is important right because when

[13:17] we take out these uh original cell from the urine or here it's very difficult to make sure the sterality in in the this biopsy right but the blood case we put

[13:29] the needles into the blood vessels we can take out the original sample without any bacteria or virus contaminations that's why we start from the blood >> okay so you're you're taking a blood cell actually so when you say you're you

[13:45] need to put the cell you need to put the proteins inside the cells right so even if you have the cells in the dish, you still need to get through the cell wall. How do you put the proteins actually into the cells?

[13:59] >> Actually, we put the DNA, the RNA or DNA into the cells. Uh because the cell has a membrane as you mentioned if you I think mixed that this DNA RNA with the

[14:11] cell, it's really difficult to put the this DNA uh uh DNA in the cells, right? That's why we are doing sometimes electroporations. It means that we are I think making a pulse of the electrons and then make a

[14:26] pulse of the electrons and then make a hole of the making a hole into the me cellar membranes in that DNA can pass through the these membranes. That's a one way or other way is we try to make some lios. It's really quite difficult

[14:43] some lios. It's really quite difficult but that's a similar I think the capsule or capset of um similar capset with the some membranes and that's coming down to the membrane they can diffuse into the me we are using chemicals I think if you

[14:56] me we are using chemicals I think if you simply say chemicals to put these DNA RNA into the cells that's also I think one of the uh that's also I think one of the uh improvement in this 20 years uh 20 years

[15:09] ago that that efficient efficiency is in induction introducing the efficiency is very low but the technology is improving we can inject more and more I think

[15:22] we can inject more and more I think yamanaka factors into the cells yamanaka factors into the cells >> okay and does it matter how much you put >> okay and does it matter how much you put in as to how much the effect is I mean

[15:34] so if one cell gets I don't know three helpings of the yamanaka factors and one gets one will it be twice as fast does it >> that's a make a difference because that's a four factors if the one is too

[15:49] much and the other is too small they can't and as you I think ask me that these cells the combination is wrong these going to the completely different these going to the completely different way for example I think gamma one of the

[16:03] way for example I think gamma one of the factor is essential to for the neurons too right because the we are using the four factor one of them is essential for the neuron. If that's too much to the cells, let's go to the neurons that that

[16:17] these four factors combination of the amount is really important to uh the amount is really important to uh the drive to these uh H0 state. So that's a important balance is important and also the entire amount is also important.

[16:32] >> Right? So let me clarify. So do you put the proteins in or you put the DNA to make the proteins? And if you put the >> the DNA or the RNA to make the proteins. >> So is it one strand of DNA that makes

[16:48] strands and you have to get all four strands in? people doing the B right one strand the DNA or separate both people is doing but the one strand case I think

[17:01] is doing but the one strand case I think that's a right because the cell get the single I think balance of the four factors right because the four factor is one each they got the only one combinations but if you change the these

[17:17] combinations but if you change the these combinations we can like control the balance of the four factor factors right that's why I think we people put the separatory two factor each or three factor plus one factor or separator four

[17:32] factors that that's depend on the methodologies but that's really key methodologies but that's really key point to uh guide these body cells to the hil cells libr stem cell yeah

[17:45] >> right and what which do you prefer I mean at eyepiece what what is your main >> yeah we are I think introduced ing a separate I think uh uh we are introducing a separate uh four factors because it's easy to control the amount

[18:00] of the uh four factors uh balance of the four factors that's why we are using a four factors that's why we are using a separate uh factors combinations okay so you you take the

[18:13] you take the skin cells you apply this you end up with 80% conversion oh so one >> our case is blood our case is blood >> oh sorry blood blood sorry yeah you that you use the blood. Um, so one of the things that you were doing is is kind of

[18:28] automating this process. Correct. >> So can you talk about that because that that sounds like I mean the thing with IPCS is if we IPSC's is if we're going

[18:40] to use them in the clinic we need to have some way of creating them in a have some way of creating them in a reliable and scalable manner. And so >> yes >> you are working on that with wi with a

[18:53] automation with you know a hardware automation can you talk about how that process works? >> Shall I share the same automation slide or automation movies? Uh yes I >> or if or I think bar yes I can answer

[19:08] >> or if or I think bar yes I can answer that because so far right because uh in the national project in the in Japan uh the Japan spend $600 million for the

[19:20] five years for IPSC research they make a five people's IPS five people's IPSC's and they make a single persons per year right in that case it's really difficult to mass manufacturing the IPSC uh to realize the future which people

[19:36] uh to realize the future which people normally have their own IPSC's right but uh and also the price is really expensive that's why I think our I think system is that we can we are making a small I think closed automation casset

[19:50] small I think closed automation casset to make IPSC the each casset we can make a personalized IPSC in each cassette once make uh once we make uh uh the once make uh once we make uh uh the person's IPSC in that casset uh we just

[20:05] remove and it trashed these casset and we set up a new cet we can make other people's in that case we can mass produced this IPSC in the automation produced this IPSC in the automation system u because so far people

[20:18] occupied huge expensive cream for a long time to make a single donors right that's a reason why that's a very expensive and also very inefficient uh but I think our system is that we are

[20:34] scale down or we we small down these big green room to the small cassette we can do everything done into the small casset that's I think our innovations to that's I think our innovations to produce the uh these clean grid IPSC's

[20:48] >> right and you mentioned personalized >> yes yes >> SC's IPSC's so how do you use these personalized how do you see these personalized IPSC is

[21:02] being used in like in the clinic or well in the clinic. So be as I mentioned in the clinic. So be as I mentioned right as IPSC can become any type of your body cells. Stem cell cannot become any body cell right neural stem cells

[21:19] become only neurons. Uh how right because for example skin stem cell can become skin or messenum stem cell is limited abilities but IPSC can become any type of body cells. The first application is a regenerative medicine

[21:35] right because if you uh get the heart vars and that people need a heart transplantation but it's really difficult to find the heart which match to your immune system. If you transplant the heart from your

[21:51] friend that will be rejected by your immune system but iPSC technologies can make a solution right because the IPSC can become any body cells it means you

[22:03] can become any body cells it means you can get your own any type of body cells as many as you want you don't worry about uh to that it means that you can lira that these tissues or cells tissues organs in the future load and in Japan

[22:19] organs in the future load and in Japan uh people succeeded to make beating uh hot cells from the IPSC's that's not anymore I think scientific fictions the first is blood and then they changed to the IPSCS and then that's IPSC changed

[22:34] to the really really beating hard cells and that's not anymore in the lab they transplanted these beating heart sheet to the heart and in the clinical trials

[22:46] to the heart and in the clinical trials and to the many peoples then they uh they the Japanese government finally approved in this er as a medications that's a historical I think time reflection point nobody have never ever

[23:02] reflection point nobody have never ever succeeded to uh make a cell product make succeeded to uh make a cell product make a other medications and but so far if they they get from now the people get the heart vars uh they can transplant

[23:15] the heart vars uh they can transplant and these the own hard heart sheet uh to the heart that's I think one application is exist start existing um from Japan

[23:27] but us too I think I think a lot of pharmaceutical company and startups try to make IPSC derived cell therapies uh they start to transplant IPSC derived cell product for example like a beta cells uh to that's a for the diabetes

[23:42] cells uh to that's a for the diabetes patient need a beta cells But d the beta cells if that they can secrete the insulins and they start these uh clinical trials and also cancer treatment too. Uh because every day we

[23:56] got the cancer cells and the immune cells attacking but then over the aging the that these immune cells getting exhausted and getting old and they cannot I think attack the cancer. But if we make when we make the IPS uh I

[24:11] delight IPS delight uh immune cells and then transplant it and the people that we can cure these cancer right that the people try to do the clinical trials even the by our hand we can see the very great u uh suppression of the cancer

[24:27] progression suppress of the cancer progression that's a first uh applications and I'd like to explain the another applications but I think I want to stop here Of course, >> but medicines.

[24:39] >> So are they using autogus IPSC's in this case or are they using IPSC's in this case or are they using them from like off the shelf? bored them from like off the shelf? bored people first using uh autoogenic first

[24:53] the other people's one because as I mentioned because so far except as uh we pe the manufacturing of the clinical grade IPS is crazy expensive but par

[25:06] grade IPS is crazy expensive but par single is a 10 million US to the 20 single is a 10 million US to the 20 million US to make a uh green go grade IPSC's that's a really very expensive that's why people try to make these

[25:22] other offtheshelf IPSC to use the medication that's the first wave is coming the answer is I think majority of the clinical trials at this time moment is the off the shelf but the beauty of IPSC is allergenic that's why I think

[25:37] our automation system try to realize that this autologus uh trans iPSC cell therapy uh because we can produce produce mass produce that these IPSC's

[25:50] produce mass produce that these IPSC's uh with the I think with that cost which people normally approach. >> Okay. And I mean how long from me giving

[26:02] you some blood to I can have some autogus uh IPSC's.

[26:14] need to make IPSC's uh because you know again iPSC uh because you know again iPSC deprogramming is time sleep uh time time travel from your body to the zel years because at least a baby need a 9 months

[26:29] in the mom's body to make a bodies if you're going back you need a couple months so that's a point that during the over the days uh culturing they start they are free program and also we need a quality control too and we check the

[26:43] quality of the IPSC's >> right >> because IPSC is basically a liver stem cells yes >> yes yes you said there was another therapy that you were going to that

[26:57] talk about that >> yes sure right because as I mentioned the one feature is iPSC's agility system iPSC's can become any type of body. So

[27:10] that's a one I think in that's that's features is useful for the one indication. The other is I think again IPSC is rejuvenated or the age librar stem cells right why don't we use these I think your own younger cells right and

[27:28] uh a couple I think 20 or 30 years ago people succeeded to do the palibiosis uh I don't know whether you know people connect the young mice with the old mice with the blood circulation system and they share the blood with the young and

[27:44] they share the blood with the young and old mice And what happened is old mice become young and but young mice getting old that's like I think drag but they

[27:56] they sh if they share that these blood that's happening that these experiments that's happening that these experiments show that if we can get the some factors show that if we can get the some factors from our own younger cells that would be

[28:09] nice we can probably digate into our bodies but how can we get our own reverted or zero age cells that's a very difficult questions but I think again difficult questions but I think again iPSCro technology can change or can

[28:24] deprogram your aged cell to the a cells so that's why why don't we use that I think IPSC's that's why we are start use extract uh of the IPSC once make your IPSC we make a uh we break the IPSC's we

[28:42] purify the extract of your own Asian librar stem cells and we start to inject librar stem cells and we start to inject these uh uh extract uh to the humans body in the clinical studies in Japan we can clearly see the rejuvenation in the

[28:59] skin hair and the whole bodies in the aging markers too. So the yes the factors from the stem cells in

[29:11] this case the the young stem cells are they does it matter whether they are they does it matter whether they are allergenic or autotogus and yeah is there an advantage to using your own cells to generate them? Yeah. Yes. I

[29:27] think uh autogress is the best because that's a of course we are using secrettorm and also I think extract of course that's not include the other

[29:39] people's cells but there are some uh small particles or these small particles protein is included first of course the immune reaction is happening

[29:52] and also other people's injection is very risky Right? Because if the person very risky Right? Because if the person is infected some virus and it's really difficult of course I think detected virus is okay we can detect the virus

[30:08] but if that's undetectable virus or unknown virus is really risky right because that's a pass through the quality control and then inject it into the human's bodies that patient getting the infectious disease for example like

[30:24] if I'm if the patient suffering HIV and then making IPSC and going back to the then making IPSC and going back to the HIV patient that's a that same virus is and then coming from that patient to the patient that's doesn't matter but the

[30:37] most difficult the risk is the that this infectious disease patient to the other people that's a really risky that's why I think I really recommend to use the their own APS-C that's not only the virus but also for the spike protein

[30:53] recently uh science identify Right. Spike protein is a a colona virus or colona bacteras syndromes after getting and then they make some small

[31:05] protein into the blood and if you get these proteins from the other peoples to get that also uh get the some colona syndrome people is concerning about that at this time moment and to short to summarize the other people's material

[31:21] the the injecting other people's material into the body is a very risky Because people doesn't want to inject other people's sweat into the into the don't want to touch the other people's sweat. But I don't know why people don't

[31:35] care about inject other people's some materials into the bodies. It's really interesting for me. >> Yes. [clears throat] Okay. So you have I So you're actually breaking the IPS-C's to um to create the

[31:51] breaking the IPS-C's to um to create the to to extract the secret. I mean, you could just extract the because I guess they're secretreting this. But in either case, iPS-C's can just keep reproducing indefinitely. Is that right? And so you

[32:07] could you could have like somebody's IPSC's and then every year or so you take some young IPS-C's and inject them into the person and just keep rejuvenating them. I mean would that seem like a plan?

[32:21] >> Yes, we are not plan. We start in Japan already first and then we uh for example like our customers 70 years uh or 80 years we uh take the blood and we

[32:33] years we uh take the blood and we rejuvenate outside of the body to make rejuvenate outside of the body to make IPSC's and we store their IPS ag stem IPSC's and we store their IPS ag stem cells into the tank once they need we

[32:46] expand we are culturing the growing up these his that person's ag body stem cells And then we make a extract from their own HD body stem cells. We we make a extract from his own ag stem cells. Then

[33:03] we inject to the at the face and head here and a knee injection and also IB2. So that's I think what we are doing in the in Japan as a clinical study. >> Okay. So that's a clinical study stage at the moment. And uh and how often do

[33:21] you in do you apply the injection? I mean >> we are injecting every two two weeks but that's called the clinical studies but in Japan in the Japanese law people can inject as a service to uh for the

[33:37] rejuvenation. Yeah. >> Right. Yeah. So, so in Japan there is a thing like the FDA doesn't have this yet where you can have like phase two is like a commercial operation where where you're a phase two trial. So you're both

[33:53] looking at efficacy but also treating like real customers. So is that where you are now? >> Yes. Yes. >> So we can Japan is a little bit different uh has a different system from

[34:08] the US. It's very interesting. Uh if we try to make a medications, of course, we try to make a medications, of course, we should go to the that uh the loot uh these uh strategy to make uh to the phase one to three. But as I think

[34:23] phase one to three. But as I think clinical research uh that we can inject these safety materials under the doctor's responsibilities as a service. So that's I think a little bit separate u uh uh law systems and that's why a lot

[34:39] u uh uh law systems and that's why a lot of uh uh uh customers or peoples coming from outside of Japan to get that these uh these uh treatment because most important things is uh followup uh after treatment right because if something

[34:55] happen people should follow up because but Japan is a medication level is very high if even if it's happening something the Japanese I think medication system can follow up that's a really important but as a safety test of course I think

[35:09] our in our materials we don't see any I think uh risk or toxicity in the in the risk uh that's why we started uh these injection as a service

[35:21] >> okay and do you so it's kind of a clinical trial do you know when it will clinical trial do you know when it will be finished will is there kind of an end date and will you be publishing the results results of this trial.

[35:34] >> Uh that's not as the doctor started published the report that these uh uh uh efficacies especially in the knees injections. Uh that's very interesting because the why people get the pain in the knees and the the the cartridge

[35:52] cells cartridge uh in the in the knee junctions is getting worse and then short smaller and smaller by the aging and that they are losing right and that's why they got the ache into knee junctions but once we inject these IPSF

[36:08] we can clearly see the rejuvenation of the cartridge they start to secrete more the cartridge they start to secrete more heal ic acid. Uh they they get lo they we succeeded to remove these pain pain from these knee junctions or we can see

[36:23] the recovery. They the doctors start to uh announce that these things in Japan but providing in this year or within year I think couple paper will be published from the doctor. >> Okay. Yeah, that is that is really

[36:39] >> Okay. Yeah, that is that is really interesting. So at the moment like if I want to kind of bank some stem cells with you or or so I could give you some blood and you would reverse it into IPCS IPSC's and then you would freeze it and

[36:54] hold it somewhere. Is that >> Yes. Yes. Correct. So we are I think if you want to do just what you should do is just take a take out the blood much I think less invasive. You don't have to I think they take out the uh skins and

[37:10] think it's really painful and so you don't have to take out the some uh fat or adiposite from your fat. You don't have to just take out the 30 minute blood is enough and then six to eight months we reprogram your body cell to

[37:25] months we reprogram your body cell to the HD body stem cells IPSS and we keep and then immediately you can use for the longevity use and if you download and if the clinical dress approved you can use you can make your own I think these uh

[37:41] uh your own body cells any type of body cells. cells. Do you clean up the sematic um Do you clean up the sematic um mutations when you're

[37:54] >> that's the most important point I think I didn't explain. Uh IPSC reprogramming can reprogram the epigenetic status but cannot reprogram DNA mutations. So that's why people should make IPSC

[38:10] into the healthy conditions. any age is fine but people should make before getting a disease that's a really important point for example I think chemosapies if they get the chemotherapy people get a lot of mutation into DNA

[38:27] after that I think we try to make iPSC it's really difficult to make this and then clean iPSC of course we try to select whole cells is not getting a select whole cells is not getting a mutations but it's more much much harder

[38:41] than making IPS in healthy conditions, >> right? So that would be a reason why you >> IPS-C's ahead of time. >> Yeah. >> Okay. >> Yeah. And also expansion too, right?

[38:54] Because the stem cells expansion also getting a lot of mutations but IPS-C's is less mutation during the expansion because the fertilized egg fertilized egg will not make a mutation into the DNA copy the IPSC2.

[39:10] If you compare the stem cell expansion versus IPSC, the mutation rate is a much less than the less less in the IPSC expansion than the in the stem cell expansion. That's also interesting. >> Yes. And if I want to turn the IP uh SC

[39:27] into a body cell, then it needs to be differentiated. Do you handle the differentiation or is is that somewhere else? Yes, that's right questions because IPSC is IPSC that's the original

[39:40] materials for the regent medicine. we should differentiate or we should change these HD stem cell to the targeted cells like such as neurons or muscles or cartridge or hair follicle or something

[39:52] like that right and we should and that's why we by in our company we are focusing why we by in our company we are focusing on to change to the uh uh immune cell to attack the cancer but we are collaborating with other companies to

[40:09] collaborating with other companies to make these and time final product or final final uh terminal differentiated cells. So because they are the variety right because the neurons or hard or other cadets there some a lot of

[40:23] variations they there are existing various type of the companies in in the world we are collaborating with them to make this final product >> interesting that you're making immune cells because like the number of a

[40:38] number of the people that I speak to say you know like rejuvenating the immune system is the basis of general rejuvenation right because the immune system seems to be so important for removing scinesscent

[40:51] cells, removing cancer >> and so that is one of the kind of areas that you're looking at. >> Yes, is correct. Right. uh as I right during the aging why they got suffering from the cancer and why they are uh

[41:05] getting old that's coming from immune cells right immune cells attacking the every day we got the cancer cells or transformed cells but immune cell attacking the these uh small cancer cells or I think tumor cells that that

[41:19] that's why we don't we don't I think suffering from the cancer but uh immune cells getting old they don't want to work anymore more they they they they they lose to attack the cancer and then the people get a cancer when they when

[41:35] they are getting old. But if we reprogram their immune cell to the IPSC and the IPSC is HD stem cells and we can reprogram we we can rejuvenate their immune cells to the IPSC and then rechange or rediff differentiate into

[41:51] rechange or rediff differentiate into their own immune cells. They got the uh dejuvenated immune cells as many as they want. Right? That's a new degation rejuvenated imunos cell therapies right so far people take out the immune cell

[42:06] from the cancer patient and they expand outside the body and then inject back to the patient but that these immune cells didn't attack a cancer that's why the patient suffering from the cancer even if you expand that these uh uh immune

[42:21] cells after suffering from cancer it's really I think a little bit I think less really I think a little bit I think less significancy to make to to cure the cancer treat for the cancer treatment. But if we can we are rejuvenating these

[42:35] uh these uh immune cells through the beard IPSC's uh we can get the more efficacy to kill the cancer. Uh that's I think a rejuvenated new immunos cell therapy and also we can you can get your own immune

[42:51] cells younger immune cells. Of course that's a cancer treatment is important but future down the road if people can use these rejuvenated immune cells as a longevities probably people can uh access the much

[43:06] longer lifespan or healthy health health span >> yes because it also clears up scesscent cells and the the immune system seems to be so important. So we touched on it before. So in so the

[43:24] FDA has just cleared life biosciences to do a phase one clinical trial with uh ER 100 which is re doing partial reprogramming. So it's not going the

[43:36] whole way but they they are using the same factors but actually they're only about that too. >> Yes. >> Yeah. So but it's much less controlled right because I am they are just

[43:50] right because I am they are just injecting a a virus well a pseudo virus with uh these factors in and we don't know how many get into which cells and >> yes >> what the issues what the concerns could

[44:03] >> what the issues what the concerns could be with invivo reprogramming >> I think I have a three concern I think try to explain a short in a short sentence one is a reprogramming, right? Rejuvenation should not be the

[44:18] reprogramming, right? Because skin cell should be skin cell after rejuvenation, right? But if you put the Yamanaka 3 factors, they start the reprogramming,

[44:31] they forgot about they are skin cells as I mentioned before, right? Because I mentioned before, right? Because rejuvenation if I rejuvenate to the five rejuvenation if I rejuvenate to the five years if I'm not be if I cannot be a

[44:44] cogi that's not I think a rejuvenation I should rejuvenate as a cogi right that's the most important point if you introduce the three factors cells start to forget about their sulfate their features so that's not anymore

[44:58] rejuvenation they become the completely different cells in that part that's a first point in the deprogramming science the programming science show that even if the that's that's happening in the

[45:12] very early stage and by the day three day two days or three days after introducing factor the already the cells start to forget about that features that's I think one of the risk that's not anymore rejuvenation that's a

[45:27] reprogramming so that's I think one of the I think a risk and they cannot maintain their own original features so that's a one risk and the second one and then we are discussing a little bit uh the deprogramming percentage is the

[45:43] program is not so high in the bodies and even in the in vitro and if you do the as I mentioned it's very difficult to control the combination of the four the control of the amount of the reprogramming factors into the bodies

[45:59] if that percent is 1% or 2% in the body what what is a 98% What happened the other I think injected cells that's become the other type of

[46:11] the random cells into the bodies it's really difficult to control that these I think a clarity or these cells I think that's a random cells that because the programming event programming scientists know the programming event is a very

[46:25] very stochastic event really random way and when that programming start is a really random so that's why if we deprogram Outside the body we can deprogram Outside the body we can control but inside the body 90% or 80%

[46:40] or 99% is a partial program or non deprogram. So it's a really difficult to control. That's the second one. It's simply say it's really has a risk for the for these for the cancer or tumors with the these transformed cells and

[46:57] it's hard is it's very interesting phenotypes. We we can see that during the uh deprogramming why the percentage is low the the majority of cells can initiate the this deprogramming

[47:11] but the over the reprogramming the majority of cell is lose the track of the this programming they try to go back to the original I think the the original

[47:23] somatic cells like if I start the blood and the majority of cells start the deepro initiate can initiate repro programming but the 90% 99% try to go back the blood cells because that they they originate blood they try to go back

[47:39] but they cannot completely go back the blood cells they go back the partially blood cells or partially something some weird cells try to go cannot go back completely if that these cells is existing in in the bodies or is making a

[47:55] existing in in the bodies or is making a bodies it's really risky it's really difficult to control the these these guys into the body that's why I think the programming scientist is really understand it's really difficult to

[48:08] control into the bodies but on the other hand but the yamaga factory injectors uh is I think that's a probably they can control with the three factor but still it's I think from my understanding it's very difficult

[48:21] >> yes well I certainly wish them luck because I I mean I really hope that it because I I mean I really hope that it works but uh yeah now one thing they do say right is so it's famously Dr. Sinclair in his lab laboratory he does

[48:35] not use CMIC >> um one of the factors. >> Yes. >> So can you talk briefly what what is CMIC and does it still work if you don't have it?

[48:49] >> Yes. So let me explain because this 20 years history is to get the approval years history is to get the approval because XBI reprogramming we remove because XBI reprogramming we remove these Yamanaka any factors uh the oxy

[49:02] for ox shimic everything we remove once we make IPS we can't see any these uh these these uh factories into the cells but people is only discussing about the

[49:14] but people is only discussing about the semic is a really uh really uh uh famous genes for related to the tumors if we overexpress the semic that's a make a risk to getting a cancer but not only the semic even the kf is also one of the

[49:32] tumor factors so that's I think as that's a not only the semic but also oxy4 is also expressing into the tumors of course tumor is expressing a couple factors and a combination is then getting tumors

[49:47] Because you know all even if you introduce the OSKM we can get the IPSC's IPSC's most I think strong feature is can grow

[49:59] uh infinitely so that that's why we can expand as many as we want and that's I think important features for the region medicine because to get the enough amount of the cell to make for example heart or neurons because we need a huge

[50:15] transplantation But on the other hand if we right because even a three factories even without seem we get that this growing cells right in into into the bodies uh that's a really risky that's a point

[50:32] because to answer your question is a cancer related gene and if we deum seem uh that's a really uh good good approach to reduce the cancer risk but that's not

[50:46] to reduce the cancer risk but that's not enough not that's not enough because OSK and especially for example like a K is I think a two modated factors uh even if

[50:58] you remove the ceic still I think the other uh risk for the cancer by expressing these yam factor into the bodies from my understanding >> okay but the reprogramming doesn't require semic to at least

[51:14] progress doesn't require but the low efficiency without seeming >> it's low efficiency. Okay. Okay. As we get to towards the end, can we look to the future? But for initially

[51:31] in the short term, how do you see the regulatory regulatory um the the regulatory environment for IP IPSC's and where do you see us where do you see that going? I mean in Japan and

[51:45] and in America, how easy is it to work with them and and do you see an immediate way of using them of g getting to the clinic? >> Yes, that's really important point. IPSC is like a probably as I mentioned IPSC

[52:00] can become any type of the body cells. It means like a semiconductors, right? It means like a semiconductors, right? IPSC is really important I think important starting material to make applications because the because for

[52:14] it's probably old like a Intel inside into the computer right because probably IPSC inside in your body in the futures right for example like I think a heart become the IPSC become hard but like a semiconductors right that that this I

[52:30] think is is future is coming it's not anymore scientific fiction as I mentioned today but but I think a layer three side of course I think for the soul applications is really is really really should be the quality of the so

[52:44] product is really important that's why I think the hard is I think of course we think the hard is I think of course we we need the is a really we that should be existing that important and that exist should be exist that these hurdles

[53:00] because that's transplant and that's I think exist for a long time into the into the life that's I think the negative side need some good need a

[53:12] control that side but that's if that's too high it's really difficult to too high it's really difficult to overcome that hurdles on the other hand cellfree uh applications like IPSC extract or these guys is a little bit

[53:26] less the risky compared to the cell transplantation or gene therapies right or or expressing a gene gen genes into the bodies. I think I think

[53:38] genes into the bodies. I think I think that we if we can that like much lower that we if we can that like much lower hurdles like to try or to approach these treatment for the longevity or or I think to treat the disease that that's

[53:52] really I think can progress this field for example like a Montana is I think is for example like a Montana is I think is changed the law if we uh uh pass through the safety data into the phase one we can make a trial these product into the

[54:08] Montana because anyway because US population is go to the Mexico or NASA or other countries to get the these cutting edge

[54:20] technologies in that case why don't we make these technology into the US with make these technology into the US with the good level of the control because the good level of the control because should not go to London injections but

[54:32] if you can try these and cutting edge techn technologies with good level of the regulations probably people can face longevity and regenerative medicines. Finally kind of looking a bit further in

[54:47] the future and sort of one question I mean reprogramming if we do systemic reprogramming which we might be able to do with these uh these secretone factors

[54:59] we're repro how how how much does that solve aging I mean are there other things that we we need to do what are the other things I mean because we have like the extracellular matrix and we have other things that go wrong that I I

[55:13] guess repro programming doesn't cover I mean what do you see for the slightly mean what do you see for the slightly longer term like 5 to 10 years

[55:25] rejuvenation I think we I want to separate two things right one is I'm separate two things right one is I'm really rejuvenate my age to the younger age that's I think rejuvenation but the other thinking if we can speed down or

[55:40] pause our aging we can get the rejuvenation For example, I'm like a 40 and if I'm still 40 body aging when we become a 50 that's I think rejuvenations

[55:53] two things is happening at least the second one probably in the in the near future people can uh get the technologies still IPSF IPSC factors our

[56:06] extract also can see that this uh phenotype and also other chemical At least of course we cannot I cannot become 5 years or 3 years it's probably

[56:19] become 5 years or 3 years it's probably difficult but at least we if we can stop difficult but at least we if we can stop or pause our age we can get the uh aging and also the the other thinking is I think we have a two I think type of the

[56:33] think we have a two I think type of the the the age right one is a healthy age and also or our lifespan the recently lifespan is around 80 years but the healthy age is 70. People should suffering from the 10 years the

[56:47] suffering from the disease or suffering from the they're facing a very very in the tough situation for 10 years in the life and the totally but if you can remove these 10 years that's also rejuvenations

[57:01] and people start to get these technologies not only the IPSC of course IPSC is good but the the other technologies and not only the medication but also for the engineing or AI I tools because if they if they cannot move they

[57:17] can thinking about which is the AI they can work with together they can enrich can work with together they can enrich their life with the technology to uh try to live with the last 10 years which they are suffering from the something

[57:31] something difficult situations so that's I think I'm I'm think that's a almost coming within the I think less than five years I I think yeah so that's a situation But if we try to people's I think I it's very interesting people's

[57:47] history is very long but we have that's a stoastic event that's why I think right people's I think the survival c is like this in that case in a like this in that case in a mathematically we should find some 5,000

[57:59] years people's 5,000 years old peoples or 10,000 years people but we can't see that these people it's very interesting people's lifespan is around 125 or 120

[58:11] is a this and then carve is completely finished. We try to elongate more than finished. We try to elongate more than the 125 is probably we need completely another technologies. I think that's nobody knows why people's surviving C

[58:28] nobody knows why people's surviving C stop I think 125 nobody knows but if we want to elongate that these more than 125 become 100 years old or 5,000 years old probably we need I think a probably

[58:42] new technology probably it's not coming soon soon >> yes yeah that is very probably true uh so Dr. Tannabe, thank you so much for joining us today. So, if people want to

[58:55] know more about your work at IPiece, where should they go? >> Uh, if you can come to our I think I'm starting YouTube too. I think if you come to or I think please search the My Peace homepage or IPS please.

[59:10] >> Okay. And I'll put links to those in the >> Thank you. >> Okay. Dr. Tanabe, thank you so much for talking with you. >> Yeah, thank you very much for giving me

[59:25] a very great opportunity to democratize the IPSC to the whole peoples. the IPSC to the whole peoples. >> Okay. Thank you.