Acceleration in iPS cells clinical applications!!

[Hairismylife]

8 sept 2015, another team have found how reprogramming cells without Oct4 factor ( Oct4 is one of the 4 factor used for iPSC reprogramming, but according to the researchers was the most critical one for possible genome instability )

http://www.cell.com/stem-cell-reports/pdf/S2213-6711%2815%2900223-4.pdf

This activator in combination with guide RNAs targeted to the OCT4 promoter can be used to completely replace transgenic OCT4 in human cell reprogramming. Furthermore, we generated a chemically controllable dCas9 activator version by fusion with
the dihydrofolate reductase (DHFR) destabilization domain. Finally, we show that the destabilized dCas9 activator can be used to control
human pluripotent stem cell differentiation into endodermal lineages.

We demonstrate that the dCas9 activator can be used to replace transgenic OCT4 in human cell reprogramming and that human pluripotent cell differentiation can be induced by the activator in a TMP-dependent manner."

In one month of discoveries, genome stability during reprogramming process is now reality

If this can speed up Shiseido commercialization then it's a good news because even with this news I think the closest treatment is still Shiseido.

[joachim]

hey lacazette, this news is fantastic.
with that iPS toolkit they are now really able to kick back mature cells to a naive cell state, by only using a naturally occuring growth factor.
now it is cheap, efficient, and also safe.

i even think with this latest tweak, the russian scientist at sanford&burham can produce much more efficient DP cells from iPS (if you remember, they said efficiency so far is not so good, they had to discard some of their iPS lines).

i really hope they are all aware of those breakthrough and reprogramming technique. i'm dieing to hear a few words on further strategy from that russian scientist. now they have all the funding and all the techniques required. the only thing left is to create millions of DP cells and try to inject them into humans finally!
we are soooo close! and still far away from commercial use.
i could sleep so much better if they finally announce efficient iPS induced hair follicles in the lab.

this made my day.

[JayM]

Hairismylife - It doesn't quite have that much to do with replicel. Unless sheishedo wan't to go down the path of using iPSC cells. It wont quicken up the process of them getting their RCH-01 to market anyway.

Lacazette - did you hear from anyone you contacted?

[Hairismylife]

hey lacazette, this news is fantastic.
with that iPS toolkit they are now really able to kick back mature cells to a naive cell state, by only using a naturally occuring growth factor.
now it is cheap, efficient, and also safe.

i even think with this latest tweak, the russian scientist at sanford&burham can produce much more efficient DP cells from iPS (if you remember, they said efficiency so far is not so good, they had to discard some of their iPS lines).

i really hope they are all aware of those breakthrough and reprogramming technique. i'm dieing to hear a few words on further strategy from that russian scientist. now they have all the funding and all the techniques required. the only thing left is to create millions of DP cells and try to inject them into humans finally!
we are soooo close! and still far away from commercial use.
i could sleep so much better if they finally announce efficient iPS induced hair follicles in the lab.

this made my day.

Is it possible to have treatment in 1 to 2 years in Russia?

[joachim]

Is it possible to have treatment in 1 to 2 years in Russia?

i don't think so. although the main researcher is russian, the work is done in florida at the sanford & burnham research center. they have to take it to japan for fastest release.

however, i could also imagine that when iPS knowledge gets more common, then other scientists around the world could theoretically replicate those procedures. it depends on how much know how is required to correctly create the DP cells from iPS. so far, the russian guy seems to be the most advanced. and he already announced that the next step is to try it on humans, but this step is at least 2 years away. only god knows why it takes that long.

but maybe those latest advancements in efficient iPS transformation could accelerate that next step a bit.

we need to get in contact with that russian scientist somehow. we need answers regarding the next steps.

[lacazette]

Hey Joachim you're right, one of the issues was that not every iPSC lines was able to differentiate in what they want, so it was hardworking and cost expensive for large DP-induced production to be clinically applicable

But now with that combo Minerva/SendaiVirus iPSCs, the 'clonally restriction' problem is solved.

The other one was safety, Terskish was saying he needed 2 years and 5M for tumorigenicity in Feb 2015 but now:

-SendaiVirus enable iPSC reprogramming with 100% chromosomal damage free
-Minerva Biotech enable iPSC reprog in a Naive state that is more clean and safe
The combo of these two companies with their worlwide aggreement is great. As they said, they are disseminate their technology to anyone who work on iPSC treatment

And there's also from august month
- the spanish team, who found how dna damage could appear sometimes(during replication stress) and found easy and cheap methods to significantly reduce the potential risk
-helsinki's team who found how to replace Oct4 factor that was the most dangerous one
-Japanese researchers who found how to switch off the iPSCs after transplantation in case of any side effects : http://insights.bio/cell-and-gene-th...ing-mechanism/

"proving it is possible to erase iPSCs on demand and demonstrating that, if side effects were to appear in therapeutic use, it would be possible to eradicate problematic iPSCs.
Lead author, Hiromitsu Nakauchi commented, “This safeguard system can eliminate contaminating iPSCs and debulk tumors originated from iPSCs.It should be applicable to other cell therapies using iPSC-derived cells. The safeguard system can be an efficient and reliable approach to provide safety for future regenerative therapy and first-in-human cell therapy.”

So this summer progresses now provide a safe way for clinically iPSCs. Terskish's tumorigenicity issue timeline is significantly reduced now.

And it seems like terskish's team plan to take advantages of Japan's regulatory like others, cause on their official S&B page, they answered to just 5% of all the comments, but answered this particularly one from hellouser

"Thomas on February 4, 2015 10:25 pm
I would donate a lot of money ONLY if the clinical trials were done in Japan as regulations there allow for quick trials as well as a quick commercial release. USA and the FDA is a waste of time. We have one life to live and I am NOT willing to wait any longer for a treatment.

Reply 
Patrick Bartosch on February 13, 2015 2:32 pm

Dear Thomas,

Thank you very much for your comment and your interest in our research. We’ll keep your contact details on file and be in touch once this moves to a stage where we can discuss clinical trials and next steps.

Best,
Patrick Bartosch
Manager, Communications
Sanford-Burnham"


If terskish enter trial in a few months, that would mean the possibility of temp approval before 2018

But they are clearly not the only hope

-Tsuji Lab needed safe iPSCs to test his 3D hair germs on humans
-One of the 3 leader researchers of Sisheido hair center is working on growing hair with iPSCs
-Keio University project already grew 3D bioengineered hair on mouse, and needed safe iPSCs aswell to go further
-Regience aswell with some of the best jap researchers
-CHA biotech from Korea who are planning iPSCs trials and have a hair project
-Sung jan lin and his 3D hair from taiwan hospital
-Singapore/P&G agreement for iPSC's therapy
-and i don't talk about Us army/thomas darling, follica, Lauster, jahoda/cristiano, chinese ones and the others

that's a hell of competition, and iPSC safety from this summer will clearly have an impact for clinical trial. And the temp approval is in place to save us really sooner than the 5-7 years we would normally have to wait

@Jay, no answers dude, maybe my questions are too much detailed and they are suspicious ^^ But be sure i will post it here whenever i have something

[lacazette]

Here is the 9 current members of Terskikh's Lab and their mails :

http://labs.sbpdiscovery.org/centerandlabs/neuroagingstem/terskikhlab/Pages/LabMembers.aspx

We should ask them about their thoughts on minerva/sendaiV 2.0 iPSCs, that can solved their safety, clonally restriction, costly, and efficiency issues and how could this impact their timeline

though, the more we approach a concrete cure solution, the more they will be secretive, so I doubt we'll have infos. Maybe someone should act like a desperate mother of an alopecia child who just want to know when they plan to test it on humans trial and what are the last issues to overcomed before it, maybe one of the lab members will give at least an average answer

[failly]

"CiRA, Hitachi to produce, store iPS cells from healthy donors for research"

september 8, 2015

"To advance stem cell research, Kyoto University's Center for iPS Cell Research and Application (CiRA) and Hitachi Ltd. will be producing induced pluripotent stem (iPS) cells from healthy subjects and storing them in a cell bank.

CiRA and Hitachi said on Sept. 7 that they will be producing iPS cells from blood donated by healthy subjects to store at the Riken BioResource Center's Cell Bank together with anonymized data of the donors' medical records.

The institute and company will start searching for subjects for the project at the Hitachi Health Care Center in Hitachi, Ibaraki Prefecture, around mid-September. They plan to gather about 100 subjects from a wide range of age demographics.

The stem cells will then be produced by CiRa, which will also pay for the expenses.

CiRA is currently heading a project to deposit to the Cell Bank iPS cells made from patients suffering intractable illnesses to help identify the causes of their conditions and produce new treatments.

With the addition of the stem cells from healthy subjects along with their medical histories and other data, researchers can compare these cells to those provided by patients."

[JayM]

Hey lacazette. Search up Biobots and see what you make of it, you seem to know more than me. But it is a 3D biological printer from the university of Pennsylvania which rings a bell as it's the same uni as Follica and they obviously have a huge Biology/lifesciences department.

[lacazette]

Hey jay their printer is pretty impressive. as they say, bioprinter used to be big and costly machine with the need of technicians,etc. And like computer progress, now they make low cost, small and even more efficient machine that any researcher in the world could buy and use easily. that's a big step for future easy clinical applications
Some researchers already have the knowledge to bioprinted skin with hair follicles, but we definitly need big manufacturing progress like this biobots to make these knowledge become reality and applicable for large population

At least if wounding neogenesis fail, cotsarelis will make a quick turn in 3Dbioprinting world with his colleagues

[lacazette]

Earlier state and chromosomal damage free iPS!

https://www.minervabio.com/news/minerva-granted-worldwide-license-to-sendai-virus-technology-for-stem-cell-generation/

WALTHAM, Massachusetts and Tsukuba, Ibaraki, Japan, August 27, 2015

Minerva Biotechnologies and ID Pharma Co., Ltd. (formerly DNAVEC) announced today that they have signed an agreement granting Minerva worldwide rights to use and commercialize their non-integrating Sendai virus vectors, together with Minerva’s proprietary technology, for generating Induced Pluripotent Stem (iPS) cells. Sendai virus enables delivery of genes into a host cell without permanently altering the cell’s chromosome, which is critical for stem cell therapies. Professor Shinya Yamanaka, MD, Ph.D., won the Nobel Prize for Medicine in 2012 for his discovery that four genes can reprogram an adult’s cell to go back in time to become that person’s own stem cell. Minerva Biotechnologies discovered a naturally occurring, primitive growth factor that continues this reprogramming to an even earlier, embryonic-like point called the ‘naďve’ state.

Scientists believe that because these earlier, naďve stem cells have a clean slate, they are more easily directed to develop into functional mature cells, which could be used for transplant. Naďve stem cells have several advantages over currently available stem cells (known as ‘primed’ state). These advantages are important for the future of stem cell therapies. Naďve stem cells do not yet have DNA methylation marks that commit the cells to certain developmental decisions. Additionally, naďve stem cells have a much higher cloning efficiency than primed state cells, which is critical for the realization of stem cell based gene therapies. Importantly, only naďve stem cells can contribute to the generation of chimeric animals. A futuristic stem cell therapy, which may not be that far off, is the generation of human-non-human chimeras that would express some human tissues or even entire human organs, for transplant.

Minerva’s proprietary primitive stem cell growth factor dramatically increases the efficiency of making human iPS cells, which greatly reduces the time and the cost of making iPS cells for research or for personalized stem cell banking. A problem that currently plagues the stem cell field is that although protocols have been devised that direct stem cells to mature into specific cell types, not every iPS cell line can mature into any cell type. As a consequence, researchers have to test many stem cell clones to determine which ones can form heart cells, which ones can form liver cells, etc. This problem is called ‘clonal restriction’ and would make personalized stem cell therapy impractical. In contrast, human iPS cells generated with Minerva’s technology are not clonally restricted; each of our human iPS cell clones has been demonstrated to have the ability to mature into heart cells, liver cells or neural cells. Minerva’s naďve state human iPS cells, or mature cells generated from, can be rapidly and inexpensively generated for use in basic research, drug toxicity testing or for personalized stem cell banking.

The agreement with ID Pharma Co., Ltd. allows Minerva to generate and sell naďve state human iPS cells as well as mature cells derived from them for research, drug toxicity testing and for personalized stem cell banking. Minerva Biotechnologies is the first company to generate human naďve state iPS cells using a single, naturally occurring human stem cell growth factor. Previous attempts to grow human stem cells in the elusive naďve state, which used ****tails of biochemical inhibitors and mouse growth factors, were prone to develop abnormal karyotype. Naďve stem cells generated with Minerva’s primitive growth factor have normal and stable karyotype. The generation of iPS cells from adult skin or blood cells does not involve the use of embryos and so does not invoke ethical issues.

“The agreement with ID Pharma Co., Ltd. provides Minerva with a powerful combination of technologies that will advance the study of basic science as well as accelerate the timeline to clinical applications of regenerative medicine,” said Dr. Cynthia Bamdad, CEO Minerva Biotechnologies. “We are very excited about our relationship with ID Pharma Co., Ltd. that allows us to disseminate our technology to others.”

“We have developed cell reprogramming kit based on our SeV vector technology as CytoTune®-iPS which could generate chromosomal damage free iPS cells easily with high efficiency. Now, the kit is well accepted in the field of stem cell research.” said Mr. Toyotaka Mori, Chairman of the board of ID Pharma Co., Ltd. “With the Minerva’s technology, we hope the iPS cells using CytoTune®-iPS technology will accelerate the development of regenerative medicine for unmet medical needs. That is very exciting.”

If you combine the two, it's really powerful stuff. More safe, more cheap, more easy, more fast, more everything hehe

10 sept 2015
The NYSCF Global Stem Cell Array™ Brings Precision Medicine One Step Closer to the Clinic

http://nyscf.org/news/nyscf-press-releases/item/1851-the-nyscf-global-stem-cell-array%E2%84%A2-brings-precision-medicine-one-step-closer-to-the-clinic

http://www.wellsphere.com/general-medicine-article/customized-stem-cells-enable-anti-aging-r-d/2178752

NYSCF designed and has built a revolutionary, high-throughput robotic platform that automates and standardizes the process of transforming patient samples into stem cells. This one-of-a-kind system addresses challenges that face the entire field, and is now an essential resource that NYSCF provides in collaborations with leading academic and industry partners around the world.

In a paper published by Nature Methods, NYSCF scientists demonstrate the breakthrough means by which the NYSCF Global Stem Cell Array™ automates and standardizes the entire process of generating patient-specific stem cells while reducing variability from manual manipulations.

For the first time ever, the NYSCF Arrray technology gives researchers the scale to look at diverse populations and draw meaningful conclusions enabling scientists to better understand the underlying causes of disease and, ultimately, create individually tailored treatments for patients.

“We demonstrate that automated reprogramming and the pooled selection of polyclonal pluripotent cells results in high-quality, stable iPSCs,”

It's all in the hands of Japan's government now(or other asians), when they will give authorisations to test growing hair on human :
-Shiseido with Dr. Manabu Ohyama
-Regience with Fujiwara and Osaka univ
-S&B with Terskish
-Riken with Takashi Tsuji ( riken had the first gov authorisation in 2014 for macular disease, and at that time it was dangerous iPSCs with possibles mutations)
-Keio university with Dr Amagai
-CHA biotech from Korea
-Taiwan hospital with Sung jan Lin
-Singapore IMB with Protect&Gambler
-the one in china and elsewhere that we're not aware of
-and I would add US army with rajesh Thangapazham, apparently they have something big, so I don't see why they would not plan to hit the asian market ( in fact, hit the asian market would mean millions of dollars that would come from all over the world not only from asian clients)

And remember that when one or more of them will have the gov autorisation to enter trial, we will have the possibility after 12/16 months of phase1 safety to pay to have access to the treatment under the temp approval system! Japan is a benediction!!
When the trials will begin , the 6-8 years timeline will be for lambda people who want proofs of 100% years of safety, 100% years of effectiveness, with big backing data.

But the ones of us who want hair ASAP and understand that it's still in 'trial process' even if we pay money, and understand the risks, our timeline will be 1/2 years after the beginning of trial. That's why temp app is created for. And that's why japan is the best country in the world

When i will have the cure, I will tatoo the japanese health minister's name on my heart

[nameless]

If you combine the two, it's really powerful stuff. More safe, more cheap, more easy, more fast, more everything hehe

10 sept 2015
The NYSCF Global Stem Cell Array™ Brings Precision Medicine One Step Closer to the Clinic

http://nyscf.org/news/nyscf-press-releases/item/1851-the-nyscf-global-stem-cell-array%E2%84%A2-brings-precision-medicine-one-step-closer-to-the-clinic

http://www.wellsphere.com/general-medicine-article/customized-stem-cells-enable-anti-aging-r-d/2178752

NYSCF designed and has built a revolutionary, high-throughput robotic platform that automates and standardizes the process of transforming patient samples into stem cells. This one-of-a-kind system addresses challenges that face the entire field, and is now an essential resource that NYSCF provides in collaborations with leading academic and industry partners around the world.

In a paper published by Nature Methods, NYSCF scientists demonstrate the breakthrough means by which the NYSCF Global Stem Cell Array™ automates and standardizes the entire process of generating patient-specific stem cells while reducing variability from manual manipulations.

For the first time ever, the NYSCF Arrray technology gives researchers the scale to look at diverse populations and draw meaningful conclusions enabling scientists to better understand the underlying causes of disease and, ultimately, create individually tailored treatments for patients.

“We demonstrate that automated reprogramming and the pooled selection of polyclonal pluripotent cells results in high-quality, stable iPSCs,”

It's all in the hands of Japan's government now(or other asians), when they will give authorisations to test growing hair on human :
-Shiseido with Dr. Manabu Ohyama
-Regience with Fujiwara and Osaka univ
-S&B with Terskish
-Riken with Takashi Tsuji ( riken had the first gov authorisation in 2014 for macular disease, and at that time it was dangerous iPSCs with possibles mutations)
-Keio university with Dr Amagai
-CHA biotech from Korea
-Taiwan hospital with Sung jan Lin
-Singapore IMB with Protect&Gambler
-the one in china and elsewhere that we're not aware of
-and I would add US army with rajesh Thangapazham, apparently they have something big, so I don't see why they would not plan to hit the asian market ( in fact, hit the asian market would mean millions of dollars that would come from all over the world not only from asian clients)

And remember that when one or more of them will have the gov autorisation to enter trial, we will have the possibility after 12/16 months of phase1 safety to pay to have access to the treatment under the temp approval system! Japan is a benediction!!
When the trials will begin , the 6-8 years timeline will be for lambda people who want proofs of 100% years of safety, 100% years of effectiveness, with big backing data.

But the ones of us who want hair ASAP and understand that it's still in 'trial process' even if we pay money, and understand the risks, our timeline will be 1/2 years after the beginning of trial. That's why temp app is created for. And that's why japan is the best country in the world

When i will have the cure, I will tatoo the japanese health minister's name on my heart

Will they have to put this into animal studies before putting it in human studies? Animal studies can take years too.

[joachim]

man, that's again, fantastic!
i always wondered if they will find an electronic/robotic way to automate cell culturing because only then it can be made for the mass, and that drives cost down.
also reliability and consistency can only be achieved with automated systems.
manual labor work would always lead to errors and risks.

so now, we have the first robotic automated device to do iPS stuff. i thought that alone would be a huge challenge and many years away, but they were working for many years in the background already.

i don't know where you always dig out that big news and information, but it's really amazing checking this forum and being surprised by great news from you almost on a regular daily basis. keep the good work up, man! i have a feeling you're enjoying the scientific and technological progress worldwide as much as i do. it's just awesome seeing the world/mankind improved by such great innovations.

[nameless]

I believe shiseido will roll out the cure in 2018 via ips cells as they claimed in an article last month. 2 well known ips cell researchers Dr.'s Manabu Ohyama and Jiro Kishimoto work for shiseido. After dr terskikh's success these researchers probably developed their own ipsc method with shiseido backing, hence their claim in that recent article. Btw first hair transplant was done by Japanese researchers in 1939!

I'm thinking the exact same thing.

[Desmond84]

Lacazette you are doing great work here brother. Just catching up on all your threads They're fascinating. Really got me pumped to get back into the research papers again and sieve through them. Thanks for all your hard work.