Acceleration in iPS cells clinical applications!!

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  • barfacan
    replied
    We're still a loooooong way from safe, practical human application. It's nice to get your hopes up, but it sucks when they come crashing down after years of abandoned treatment research

    Leave a comment:


  • nameless
    replied
    Originally posted by lacazette
    Joachim and Desmond, thank you guys but i don't really deserve, key words and google are the one to be grateful hehe


    Hey mikes, yep that trial is really important, it has been halted in June, but that's why we saw so many breaktroughs this summer on the particular area of "reprogramming DNA damage free iPSCS" (as every iPSCs team over the world work on this last major issue)

    At that time they found a few mutations in some cells ( even if not dangerous according to lead trial Phd Dr. Masayo Takahashi ) they halted and didn't go for the second patient to first,investigate if it was coming from the patient's disease or if it was due to the reprogramming process. Then they confirm that it was the last one. According to Dr.Takahashi, they were making a redesign of how iPSCs are produced and there are also adjustments and changes in japan's regulations in this area, detailed genetic analysis of ips lines before transplant, etc

    And according to Dr Knoepfler a stem cell researcher, when they will enter the trial again, it will be the major step forward for other iPSCs clinical

    Any idea when they will re-enter the trial? I wish they would implant the 2nd patient soon.

    Leave a comment:


  • lacazette
    replied
    Joachim and Desmond, thank you guys but i don't really deserve, key words and google are the one to be grateful hehe


    Hey mikes, yep that trial is really important, it has been halted in June, but that's why we saw so many breaktroughs this summer on the particular area of "reprogramming DNA damage free iPSCS" (as every iPSCs team over the world work on this last major issue)

    At that time they found a few mutations in some cells ( even if not dangerous according to lead trial Phd Dr. Masayo Takahashi ) they halted and didn't go for the second patient to first,investigate if it was coming from the patient's disease or if it was due to the reprogramming process. Then they confirm that it was the last one. According to Dr.Takahashi, they were making a redesign of how iPSCs are produced and there are also adjustments and changes in japan's regulations in this area, detailed genetic analysis of ips lines before transplant, etc

    And according to Dr Knoepfler a stem cell researcher, when they will enter the trial again, it will be the major step forward for other iPSCs clinical

    And i think it moves well, Dr Takahashi will receive today the inaugural Ogawa-Yamanaka Stem Cell Prize at the Gladstone Institutes in San Francisco

    The Gladstone Institutes is pleased to present the inaugural Ogawa-Yamanaka Stem Cell Prize to Masayo Takahashi, MD, PhD, a faculty member and project leader in the Laboratory for Retinal Regeneration at the RIKEN Centre for Developmental Biology in Japan.


    Dr. Takahashi was awarded the prize for her trailblazing work leading the first clinical trial to use induced pluripotent stem (iPS) cells in humans.

    "It is extremely gratifying to see iPS cell technology applied in humans only eight years after its discovery," says Shinya Yamanaka, MD, PhD "I applaud Dr. Takahashi's pioneering work to advance stem cell technology and help cure ocular diseases." Dr. Yamanaka, who is the director of the Center for iPS Research and Application (CiRA) at Kyoto University, won the Nobel Prize in 2012 for his discovery of iPS cells.

    George Daley, MD, PhD, professor of hematology/oncology and director of the Stem Cell Transplantation Program at Boston Children's Hospital, says, "By confronting and ultimately solving the many regulatory challenges of a first-in-human trial, Dr. Takahashi has paved the way for all of us in the stem cell community to recognize the promise of iPS cells."

    The first surgery was successfully performed in September 2014 using retinal tissue Dr. Takahashi created from the patient's own iPS cells. Prior to moving the study to a second patient, Dr. Takahashi chose to delay the trial as part of a safety validation step and in consideration of anticipated regulatory changes to iPS cell research in Japan. This demonstrates an appropriate degree of caution applied in such research and highlights the rigor displayed by this year's recipient.

    "As both a physician and a scientist, Dr. Takahashi embodies the ideal recipient because her work brings cellular reprogramming to patients," says Gladstone president R. Sanders Williams, MD. "Mr. Ogawa's visionary support of translational stem cell research will help encourage and accelerate the progression of the field."

    (ps: they say the ceremony will be live streaming, maybe we could learn something)

    I aslo read CIRA annonced planning enter iPSCs trials for various serious diseases this coming year, aswell as CHA Korea in collaboration with Japan hospitals, and maybe others of course
    So i think this summer progresses on reprogramming make his job, and DNA safety, new regulations, etc are currently in the process to be overcomed
    let's see if Dr takahashi will say something tonight about what's goin on now

    For the lab grown follicles you talked about Mike, on the japan tv show about Shiseido/replicel, it is explained how Dr Tsuji already grow lab hair, but that with a skin biopsie ( to take the cells needed) , he can grow just 1 hair or so, when we would need more than 10000. And so that the solution is iPSCs to have unlimited cells
    differents researchers already how to grow lab hair with various kind of method, but unfortunatly the problem is the limited cells number we have

    As you posted, there's unreal progress in 3D bio engineering/bioprinting, for large real life clinical application and in our case the tools to create functionnal lab hair but the last problem is that we need that unlimited source of our own cells as a source to create a large number of hair

    And we will have soon, Minerva/SendaiVector + the robot sell by NYSCF = almost 100% of the iPSCs problems solved (and if you add the breakthroughs in august from the spanish team, the helsinki one, etc..it is going fast) It's no surprising as it's the n'1 problem in iPSC area now,and there's hundreds of the best team in the world working on it. and so they working for us hair loss sufferers lol cause we know how to grow hair, but we just need iPSCs to grow unlimited hair
    so it's the whole world science now who work to solve the last issue, we , hair loss sufferers need to overcomed to make a hair therapy possible. So in fact it's no more 50 researchers who work for our problem, but 10000+ indirectly ^^ it will move fast as we are seeing it til' july, august, sept. Im confident let's see how it goes in the comin' weeks


    I'll put the link of Yamanaka prize stream tonight, Dr Takahashi will talk about her trial

    Leave a comment:


  • Renee
    replied
    I agree with mike! I emailed them a month ago about the progress on hair loss research. I received an automatic email response from their CEO who said " I am attending a conference and will respond to emails with a delay." I never heard anything back from them.

    Leave a comment:


  • mikes23
    replied
    I believe we are moving alot faster towards a cure then we ever were before but still seems there are issues with ips cells
    http://www.forbes.com/sites/emilymul...ction-problem/

    "Earlier this month,*New Scientist reported*that the Japanese trial has been halted after genetic mutations were detected in the cells of the second trial participant. The first subject to receive an experimental iPS cell treatment, a 70-year-old woman, is reportedly healthy."

    I also came across this from the same article

    "Still, Xu acknowledges that there is yet another hurdle to overcome for the stem cell therapy to be successful. “Macular degeneration-associated inflammation can also kill cells transplanted into the lesion,” Xu said. “This would be another immune-related challenge for iPS cell-based therapy.”

    I know it's not talking about hair loss, but I wonder if the inflammation caused by hair loss is also killing these ips cells that are being transplanted?

    none the less, the article still shows how we are progressing

    "Now, a team of scientists headed by biologists at UC San Diego has discovered how induced pluripotent stem (iPS) cells, which are derived from an individual’s own cells, could be programmed to avoid rejection from the immune system."

    I think ips cells will help the medical field greatly but I still think lab grown follicles are our best chance.

    Here is a good article about 3d printing. Stuff like this may be able to help dr lauster create a terminal follicle.



    "One of the great hopes for stem cells is that they'll allow us to eventually replace injured or damaged tissues. But there's a big gap between the cells of stem cells and anything resembling an organ. Organs are complex, three-dimensional structures populated by multiple cell types. Getting a bunch of cells to form these structures is a significant challenge."

    "One idea has been to use 3D printers. With multiple print-heads and a protein polymer gel, it's possible to construct a rough approximation of the structure of a mature organ. Now, a team of California scientists has come up with an interesting alternative: use DNA as a sort of cellular velcro to get cells to stick to each other and form a complex, three-dimensional tissue."


    I also emailed Dr lauster to see if they would be attending the hair loss conference. But Desmond if you have time could you get in contact with them? I'm thinking if they don't go to the Conference then they might be done with lab follicles. So I'm hoping you could rule that out by asking them. Or they might have solved it and don't want to give out to much information to the competition. I remember you saying it seemed like they were holding something back from you. I would email him and ask but I figured, one if we all keep emailing him he will stop responding....two, you are already familiar with him, so he might reveal more information to you. It just seems strange that one of the top hairloss doctors wouldn't have his team attending the world hairloss conference.

    Leave a comment:


  • failly
    replied
    Nucleoside Supplementation Reduces Genomic Damage in Induced Pluripotent Stem Cells

    "Nucleoside Supplementation Reduces Genomic Damage in Induced Pluripotent Stem Cells"

    14 september 2015

    "Spanish researchers have described a method to reduce the amount of genomic damage incurred during the process that transforms mature adult cells into induced pluripotent stem cells (iPSC), thereby making them potentially useful for biomedical applications.

    The reasons behind the genomic instability observed in iPSCs remain mostly unknown. Investigators at the Spanish National Cancer Research Center (Madrid, Spain; www.cnio.es) recently suggested that this genomic instability was similar to the phenomenon of oncogene-induced replication stress, and that the expression of reprogramming factors induced replication stress.

    Replication stress is defined as slowing or stalling in DNA replication fork progression. It arises from many different sources, which are considered as replication barriers such as telomeres, repetitive sequences, DNA lesions and misincorporation of ribonucleotides, secondary DNA structures, DNA–RNA hybrids, dormant replication origins, collisions between replication and transcription complexes, hypo-acetylation and compaction of chromatin, early-replicating fragile sites (ERFSs) and common fragile sites (CFSs). Overexpression or constitutive activation of oncogenes has been cited as an emerging source of replication stress.

    The Spanish investigators reported in the August 21, 2015, online edition of the journal Nature Communications that increasing the levels of the protein checkpoint kinase 1 (CHK1) reduced reprogramming-induced replication stress and increased the efficiency of iPSC generation. Similarly, nucleoside supplementation during reprogramming reduced the load of DNA damage and genomic rearrangements during the iPSC generation process. The data revealed that lowering replication stress during reprogramming, genetically or chemically, provided a simple strategy to reduce genomic instability in mouse and human iPSCs.

    First author Dr. Sergio Ruiz, a researcher in the genomic instability group at the Spanish National Cancer Research Center, said, "Based on previous research performed by the group, we knew that an additional input of nucleoside reduces replication stress, probably by facilitating the successful replication of DNA as it increases the rate of cell division during the reprogramming process."

    Leave a comment:


  • Desmond84
    replied
    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.

    Leave a comment:


  • nameless
    replied
    Originally posted by Renee
    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.

    Leave a comment:


  • joachim
    replied
    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.

    Leave a comment:


  • nameless
    replied
    Originally posted by lacazette
    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




    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.

    Leave a comment:


  • lacazette
    replied
    Originally posted by lacazette
    Earlier state and chromosomal damage free iPS!




    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 ‘naïve’ state.

    Scientists believe that because these earlier, naïve stem cells have a clean slate, they are more easily directed to develop into functional mature cells, which could be used for transplant. Naïve 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. Naïve stem cells do not yet have DNA methylation marks that commit the cells to certain developmental decisions. Additionally, naïve 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 naïve 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 naïve 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 naïve 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 naïve state iPS cells using a single, naturally occurring human stem cell growth factor. Previous attempts to grow human stem cells in the elusive naïve state, which used ****tails of biochemical inhibitors and mouse growth factors, were prone to develop abnormal karyotype. Naïve 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




    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

    Leave a comment:


  • lacazette
    replied
    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

    Leave a comment:


  • JayM
    replied
    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.

    Leave a comment:


  • failly
    replied
    "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."

    Leave a comment:


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



    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

    Leave a comment:

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