Challenge could cancel Yamanaka iPS cell patent

Yamanaka Patent challengeA new patent dispute has exploded in the stem cell field.

What’s going on?

In 2006, Shinya Yamanaka reported cellular reprogramming to create mouse induced pluripotent stem (iPS) cells in Cell and the next year multiple groups along with Yamanaka’s reported creating human iPS cells.

It’s no exaggeration to say this was a blockbuster development for the cell and developmental biology fields and Yamanaka later went on to win the Nobel Prize for this discovery.

Another element to the iPS cell story is the intellectual property (IP) related to iPS cells.

There have been numerous IP claims and patents related to cellular reprogramming and iPS cells, but the dominant patent has been U.S. Patent No. 8,058,065 to Yamanaka et al. that was issued on November 15, 2011, which has been commonly known as the “Yamanaka Patent”.

The common perception in the stem cell/regenerative medicine field has been that the cellular reprogramming sector would be mostly dominated at the IP level by the Yamanaka Patent despite there being other patents in this arena.

However, I just learned of a serious challenge to the Yamanaka Patent, which could really turn things upside down. I predicted an iPS cell patent war back in a post this May.

The iPS cell patent challenge was filed by a mysterious entity called BioGatekeeper, Inc.

What is BioGatekeeper? Read on on Page 2!

66 thoughts on “Challenge could cancel Yamanaka iPS cell patent


  1. I think that any speculation regarding the outcome of this litigation is extremely premature, especially without a full analysis (not the oversimplified comment of an “anonymous legal guru”). However, the identity and intentions of the mysterious BioGatekeeper are certainly interesting.


    • When something like this comes up it seems entirely appropriate to think its implications and possible outcomes. What’s your take on the patent challenge document? Hopefully I will know soon who BioGatekeeper is, which could also shed significant light on their intentions, etc.


      • I agree that it is useful to consider the implications and possible outcomes (especially considering that regardless of the present outcome there will likely be implications for the field); I just meant that it is premature to make any actual predictions given the limited information available and the many variables that can affect the final outcome. As for the challenge, as summarized in your post it appears to be based on the allegation of obviousness. However the analysis to determine patentability is not as simple as suggested by your anonymous guru, as secondary considerations such as unexpected results, successful commercialization, established need, etc may still establish patentability even if obviousness is established, and the obviousness itself will also likely be debated. Additionally, during prosecution, the examiner may have already applied this same rationale of obviousness to reject, and such a finding of obviousness may have already been overcome by Yamanaka et al. It would be interesting to go back and look at what the final grounds for patentability actually were. My point was just basically that without a detailed analysis of all available information, it is difficult to make any reliable assessments. As for BioGatekeeper, please do keep us posted with your super sleuthing! It will be interesting to see if it is someone with “altruistic/open-source” motivations, such as patient rights activists or basic researchers, or perhaps someone with a financial interest, such as someone else who wants to operate freely in this space (or someone whose own iPS patent application was rejected?). Given the very low profile of all of this, I would be tempted to guess the latter…but really have no idea.


        • Given where the legal representation is based, I think it might be someone associated with PrimeGen Biotech. It seems incredibly hard to find any real internet presence for them any more. They do have a patent claiming to make pluripotent stem cells from primordial germ cells via chemicals, which would go along with Shinsakan’s suggestion of someone who want to operate freely.


            • Very interesting- good eyes, Larry! The ex parte reexamination for Jaenisch just says that the attorney was the requester, so it is not possible to know who was actually behind it. However, the law firm used for the Jaenisch re-examination request specializes in intellectual property and is different from the one used for the inter partes review of Yamanaka (although both law firms are from Orange County, CA). Additionally, one thing to note is that the ex parte reexamination request was filed on 3/31/2011, i.e., about a year after the Jaensich patent was issued. In contrast, the intra partes review petition for the Yamanaka patent was filed 8/12/2014, i.e., almost 3 years after the Yamanaka patent was issued. Why wait so long? I would think that if it were the same entity that they would try to kill the Yamanaka patent as soon as possible if they had already tried to invalidate Jaenisch. These differences make me think they are unrelated, but who knows? One thing to think about, though, is that Rongxiang Xu seems to have been fixated on Yamanaka (not Jaenisch) for some time, and that his civil suit for slander, defamation, etc. against Yamanaka was thrown out of court earlier this year (i.e., a few months before the inter partes review request was filed)- he was also ordered by the civil court to pay Yamanaka’s attorney fees only 6 days before BioGatekeeper was formed, which was only 11 days before the inter partes review petition was filed. To me, that timing is suspicious, especially given the long interval between the issuing of the Yamanaka patent and the filing of the inter partes review. Just saying…


              • Your investigative skills are much better than mine, Shinsakan.

                Just to add to this, MEBO international published a notice to their website on August 14th, 2014. I found this when I was looking for the patent porfolio.

                I then made the mistake of reading the notice. I will never ever get that time back.


              • Civil case against Yamanaka was thrown out of court with prejudice. Xu has to pay Yamanaka ~$90,000 for attorney fees.


              • This case was Xu vs. Yamanaka, not the other way around. Yamanaka would have to separately sue Xu for “reputation damage” to seek the compensation you are talking about. But think about it realistically: why would he do that? His reputation was not actually damaged (Xu’s accusations seem kind of like a joke; the court certainly thought so) and Yamanaka is too busy doing actual research and actually contributing to the field of regenerative medicine to pay attention to something minor like this. He is a world-renowned scientist and Nobel Laureate. Something like this is fun to laugh at but would obviously not affect his reputation, When Xu’s lawsuit was thrown out, Yamanaka just asked the court to make Xu pay his lawyer fees because Xu dragged him into court for no reason, and it would not be fair for Yamanaka to have to pay for it.

                http://docs.justia.com/cases/federal/district-courts/california/candce/4:2013cv03240/268145/46


          • The principal is just the a legal rep. In Nevada you can incorporate and the shareholders can remain completely anonymous. E.g. the legal rep in this case is president, treasurer, etc. Certainly has no background in stem cells and in located in CA. I forget where else this is allowed in the US but Nevada is special since Las Vegas/goodfellas and all that. Interesting approach.


  2. I’m guessing BioGatekeeper is just a newly formed a Patent Assertion Entity representing the patent holder if they haven’t already purchased those rights.


    • Thanks for the comment, DC. That could well be it.
      What would the patent holder be though?
      The main institutional one mentioned in the document is Whitehead, which has indicated they are not involved.


      • My understanding is the Inter Partes Review process allows for third parties (non patent holders) to initiate the review. Perhaps BioGatekeeper is looking to court Whitehead on the basis of showing reasonable likelihood of prevailing?


      • From the petition, the Whitehead patent seems to be only being used because it specifically mentions using introduced genes for reprogramming. The petition tries to paint the Yamanaka factors as totally obvious, as opposed to, oh, say, chemicals. which are totally not obvious. /eyeroll

        My money is on PrimeGen being the patent holder. Speculation: They probably think their portfolio is pretty rock solid (cryopreseravation patent awarded on August 7th) and that the only thing holding investors back from giving them lots of money is the Yamanaka patent.


    • This is an interesting idea, as we have not really seen much patent troll activity in the life sciences. However, typically, Patent Assertion Entities seek to do just what their moniker suggests and assert patent rights by suing infringers to make money- in contrast, in this case, at least at first glance it seems that the purpose of the litigation is to invalidate a patent owned by someone else, and not to actually directly assert patent rights.


  3. Abstract of “The Real Road Blockers for Patenting iPS Cells” (Logical Biology 8 (2):62-65, 2008)
    The unproven claim of “inducing” pluripotent stem (iPS) cells has even been written into a patent application by Yamanaka et al. However, once the hypes surrounding the iPS cells are removed, it will be shown that the so-called iPS cells made so far are just some man-made cancer cells. Future efforts of making cancer-free iPS cells may need to rely on some chemicals that activate the pre-existing stem cells and/or progenitors. If that is the case, then some prior arts developed by a Chinese physician will be real road blockers for others to patent their therapeutic iPS cells because Rong-Xiang Xu has already obtained some patents on using chemical compositions for in situ activation of regenerative stem cells and has shown some clinical evidences of in vivo cloning of tissues/organs. See complete publication at http://im1.biz/albums/userpics/10001/LB2008V8N2A6_Patent.pdf


      • Paul is right. There is no doubt that adult cells, in vitro, can be turned into pluripotent stem cells, in vitro. We’ve done it hundreds of times using Shinya Yamanaka’s methods.

        Efficiency is irrelevant because we don’t need a hundred iPSC lines from the same person.

        We can argue all day about whether pluripotent stem cells exist in nature, as blastomeres and inner cell mass.


        • Efficiency is not only relevant but also critical to this argument on whether Yamanaka’s iPS reprogramming can “induce” (terminally differentiated) adult non-stem cells into (embryonic) (pluripotent) stem cells. As adult body contains pluripotent stem cells in many tissues and theses existing stem cells can be selected out for proliferation, it is key for any pluripotency-“induction” claim to demonstrate its reprogramming method can work well on ALL cells and thus “induce” pluripotent stem cells from non-pluripotent cells at a high efficiency. But what is the reprogramming efficiency of Yamanaka’s reprogramming method?


          • If reprogramming is not actually being induced, then why does culture of the same cells (e.g., MEFs) under the same conditions but without expression of the Yamanaka factors not result in spontaneous iPS colony formation? If “adult body contains pluripotent stem cells in many tissues and theses existing stem cells can be selected out for proliferation” and these cells were merely being selected by culture conditions, there should be spontaneous iPS colony formation without transduction of the Yamanaka factors. This does not occur. The reprogramming is induced by transduction of the Yamanaka factors. The induction of reprogramming and the efficiency of reprogramming are two totally separate issues.


    • The patents have already been issued; therefore, the “prior arts developed by a Chinese physician” are actually not “road blockers.” Also note that in the inter partes review request discussed here (which to date is apparently the only legal challenge to any iPS patent and has yet to be even approved for an actual review), the work of the individual in question is even not cited as prior art and thus seems to be irrelevant.


      • They would be road blockers had Nature Biotechnology published my paper in 2008. However, the points made in my paper are still valid even today.


  4. I’m now leaning toward Rongxiang Xu as the identity of Biogatekeeper. Shinsakan’s right- having the same attorney is unlikely to be a coincidence. However, Jaenisch’s patent is at the center of the argument, and overturning Yamanaka would benefit Jaenisch the most. Fate holds that patent.


      • Where exactly in the Xu patent is there anything even remotely related to the present discussion? It seems irrelevant, which is likely why it was not cited as prior art in either the Yamanaka or Jaenisch patents and also not even cited in the in partes review request challenging the Yamanaka patent. The Jaenisch patent number was given by Dr. Knopfler in his post above; it is also referenced in the inter partes review petition being discussed here.


      • Not to be picky, but I think the word “reported,” is a bit misleading there. This is a paid advert. I mean the main contact is a PR firm. I also wouldn’t call it a prestigious European prize. It’s just a small economic club with a few hundred members in Slovakia from what I can tell. The award they gave Putin was for, “most likable leader. “


    • I still think that PrimeGen Biotech is the identity of Biogatekeeper.

      If it was Rongxiang Xu, his past actions lead me to believe his name would be all over this. He would more than likely want everyone to know that he got Yamanaka’s patent overturned. Because of course there’s no such thing as bad publicity.

      Another kind of outside possibility could be Shi V. Liu. He seems like he has an axe to grind against Yamanaka. He’s an outside possibility because he seems to question the very idea of iPSCs, whereas the petition is isn’t questioning that, but rather that the invention was obvious. However, this doesn’t rule out him acting out of a somewhat deluded sense of justice in science.

      This smells like a typical electronic tech sector ploy: eliminate competition by destroying their patents. This particular law firm has already shown that they are willing to file against Yamanaka and they’re located in Irvine and so is PrimeGen.


      • It is very inappropriate to characterize my effort of seeking truth and thus serve justice in science as some “deluded sense”. As an outsider I should have more common sense than those insiders whose views might have even being strongly influenced by various conflicts of interest. These political arguments putting aside we should focus on this discussion whether Yamanaka’s research team had indeed “induced” (terminally differentiated adult non-stem) cells into (pluripotent embryonic stem) cells and thus deserve the patent. For this reason I would even disregard all the speculations on who is behind the challenge, whether it has a Wisconsin connection or an Irvine tie.


        • The aspect of the validity of the Yamanaka patent being challenged by BioGatekeeper is not whether or not Yamanaka has induced cell reprogramming. This is not under debate, and not challenged by the petition; it is not an issue. Rather the petition alleges that Yamanaka’s successful cell reprogramming would have been obvious to do based on Jaenisch. It would probably be most productive to focus the discussion on what is actually at issue.


          • Hmm, looking at the claims in the Jaenisch patent, the invention is the Oct-4-GFP reporter cells and mouse (feel free to correct me if I’m wrong), whereas the invention in the Yamanaka patent is a specific set of retroviral vectors and the way of growing them on specific substrates. Additionally, the Yamanaka patent shows that this vector combination reprograms human cells. This was, to me, unquestionably non-obvious at the time of filing.


            • Yamanaka is drawn to a method; Jaenisch is drawn to a composition. Other differences aside, Yamanaka is essentially drawn to a method of specifically expressing exogenous Oct3/4, Klf4, c-Myc, and Sox2 to achieve reprogramming. Jaenisch is drawn to a somatic cell that specifically expresses one exogenous gene (Oct4, Nanog, or Sox2; not the combination) in the same composition with a “candidate agent of interest with respect to its potential to reprogram a somatic cell (this seems to be where the small molecules come into play),” without actually indicating that reprogramming occurs. In terms of the rest of the disclosure (i.e., outside of what is claimed), it is interesting to note that although the Jaenisch patent talks about reprogramming using genes, it only actually shows data for the combination of Oct4 overexpression with nuclear transfer of fibroblast nuclei into oocytes. In my opinion, Jaenisch therefore really seems to be more related to enhancing SCNT/cloning by overexpressing stemness genes than to iPS per se. In contrast, the Yamanaka patent actually presents data to show reprogramming of fibroblasts to stem cells (without requiring nuclear transfer/SCNT).


        • I thought those were your posts.

          First, your seeking truth in this case disregards not only all the replications done on generating iPSCs from fibroblasts, but also the verification studies carried out by the Jaenisch lab and the studies using purified populations of cells. As Paul and Jeanne have stated to you above, this is proven. One is simply not selecting for some pluripotent adult stem cell that has somehow persisted through development. Terminally differentiated adult non-stem cells are reprogrammed with the Yamanaka factors and continue to remain so if the vector is removed from those cells after reprogramming.

          Second and much more importantly, your claim that the patent hinges on whether or not the cells were induced at all is not what the petition is about at all. The petition is essentially making the claim that the invention was obvious to the whole stem cell field at the time, and thus not patentable. I personally disagree with this claim made by the petition.


          • Could you please give some references for the publications which have proven the induction of pluripotent stem cells from terminally differentiated cells?


    • Very interesting point, Dr. Loring- I agree, but I do wonder about how much the Yamanaka patent actually affects the Jaensich/Fate at present, as what the claims actually cover seems to be very different between the Yamanaka and Jaenisch patents. How much benefit would Jaenisch/Fate actually derive from invalidation of the Yamanaka patent? Is it actually blocking their present or planned activity? I was under the impression that they were more interested in applying small molecules/peptides or other external factors for reprogramming; the Jaenisch patent claims appear to reflect this. Just wondering…


      • I agree with Shinsakan. Fate seems to be pushing their Wnt7a analogs much harder than their iPSCs. It seems like they’re using the iPSCs more as a drug-screening platform rather than a cell therapy.

        Maybe the Jaenisch patent is all they need?


  5. Not having read the original patent, but just being made aware of this new challenge, I must add another dimension to the Yamanaka feat. While I personally feel that what Yamanaka’s team did was not only a creative experiment but that it was an heroic exercise in the production of a “so-called” induced pluripotent stem cell. However, my challenge has been that these “so-called” iPS cells, while real, have been misinterpreted as to their origin. I have published several peer-reviewed, but rarely cited, papers providing another interpretation that these cells’ origin are not differentiated somatic cells that were “re-programmed”, but they were derived from preexisting adult organ-specific stem cells. All my “Letters to the Editor” to Nature, Science, etc. were always rejected. Even my multiple correspondences to the Noble Committee have never been acknowledged.

    My lab’s background and experience in the mechanism and origin of human cancers, plus the fact my lab was the first to isolate human organ-specific adult stem cells (1987), provided me with experience to explain why “reprogramming” of somatic differentiated cells in vivo could not explain the origin of cancers. Therefore, we ventured to isolate existing organ-specific stem cells to test the stem cell hypothesis of carcinogenesis. In our paper, using normal human adult breast stem cells, my colleagues and I showed that the adult breast stem cell, but not the differentiated breast epithelial daughter cells, were the “target cells for breast carcinomas [ see Tai, M.H. et al, Carcinogenesis, 2005].

    In summary, the decades of research in the cancer field , including the many failures to “immortalize” normal human fibroblasts in vitro, provided a valid, rich history for the reason the “stem cell hypothesis” of cancer seems to have convinced most in this field that the “de-differentiation” or “reprogramming” hypothesis simply did not have experimental support.

    In the end, I am not challenging the fact that the Noble Committee should take back the prize from Dr. Yamanaka, because he deserved it for the technical feat of isolating this unique cell. I am challenging the Committee and the scientific community to consider the alternative hypothesis that these “iPS” cells are originated from preexisting organ-specific adult stem cells. Since the rigorous resolution of this challenge has not yet been done, if my interpretation is correct, then this original patent might have severe limitations.


    • It is very sad that “mainstream” scientists especially those active in “top” journals have willingly or intentionally neglected compelling alternative explanations for the “induction” of pluripotent stem cells. I was one of the earliest “sidestream” scientists who publicly identified the iPS cells as incorrectly programmed stem cells (still abbreviated as iPSCs though, just for consistence in terminology and efficiency of search all relevant iPS research literature. More frankly or harshly, I pointed out that iPSCs are man-made cancer cells. I welcome any challenge to such discovery but I wish all criticisms on my claim be made with real names in truly scientific ways.


    • Now this is really interesting.

      Against my better judgement, I went poking around on the MEBO International website, specifically in the patent section. The correspsondence address listed on the first US patent for RongXiang Xu’s stuff matches up with a law office in Palo Alto, CA, where, get this, one can find this attorney’s page:

      http://www.wsgr.com/WSGR/DBIndex.aspx?SectionName=attorneys/BIOS/11152.htm

      Looking at this, I now agree with Jeanne. Rongxiang is now the frontrunner in my mind.


      • I was originally thinking the exact same thing as you when I saw that name pop up. However, the law firm that originally prosecuted Xu’s patent is one of the most legendary, elite tech law firms in Silicon Valley (they handled the IPOs for Google, Apple, Linkedin, etc.). If BioGatekeeper were associated with someone of that level, then I would expect for them to also use a heavy-hitting law firm with patent expertise and experience for the inter partes review petition to give it the best chance of success, rather than the law firm that BioGatekeeper has actually hired. Additionally, I wonder whether a partner in a high-profile law firm would also be allowed to be the president/named officer of another company. Furthermore, Palo Alto is pretty far from Los Angeles, although that may not mean anything. Then again, who knows…maybe choosing a small, relatively unknown law firm from outside the patent world is a way to help preserve the anonymity?


        • I’m thinking it’s possible that this is being done as a favor for Rongxiang, i.e., the Palo Alto law firm wants nothing to do with this, so Biogatekeeper could be essentially a shell company. Although that would be a pretty big favor. It’s also possible that the people in involved just happened to share the same name: two Jonathan Zhu’s and not connected.

          According to Bizpedia, the address listed on the Nevada site is already occupied by Global Tech Staffing Unlimited LLC. Can’t really find anything else on them at the moment.

          As for the anonymity aspect, I think you might be right. Also, as you pointed out before, the small firm handled Rongxiang’s previous case.

          I think it’s also worth considering that just because the small firm filed the patent, that doesn’t necessarily mean they actually wrote it.


          • Whoops, that last mention of “patent” should be “petition”.

            My mistake.


          • Very interesting idea, and I do agree with you that it is probably a shell company- but if I were a partner in a high-profile law firm (especially if my bread and butter was tax law and investments), I wouldn’t want to put my name as the sole officer for a seemingly dubious shell corporation. It would be easy to find someone else to put their name there instead. I think it is more likely that the two individuals are not connected, but who knows?

            I also looked at who/what else might be at that address- it looks like a set of offices in a loft complex in downtown LA. In addition to Global Tech Staffing, I also found a completely unrelated attorney’s office. I think these are probably just unrelated business that are either previous tenants or using the same office space.

            As for the small firm not writing the inter partes review petition, I agree with your idea in principle, especially if we are getting to talking about shadow companies and whatnot, but from reading the actual petition, it seems pretty clear that the small firm wrote it without help; I would be very surprised if it were ghostwritten by someone else.


              • Because it’s fun and provided some entertainment for the weekend- this is like reality TV. There really isn’t much to talk about for the petition itself.


    • Oops, I missed you found the incorporation info when I posted my comment. Frankly it’s just a shell company. You can put whatever name you want on it, even just hire someone for the sole purpose of being the president of your new fake company. But, with the same law firms used, similar language about how it’s misleading to call them stem cells in both this and the Nobel lawsuit, plus the company info (as far as I can tell it’s registered to a FedEx), I’m strongly leaning towards Xu (XXXXX comment edited)


  6. In response to truth4science:

    “If adult body contains pluripotent stem cells in many tissues and these existing stem cells can be selected out for proliferation” and these cells were merely being selected by culture conditions, there should be spontaneous iPS colony formation without transduction of the Yamanaka factors. This does not occur.

    First, it is a fact that the so-called iPS cells are never completely “re-programmed” and always have epigenetic markers of the target tissue from which the iPS cells were derived.

    Second, it is a fact that organ-specific adult stem cells do exist in in vivo and have these epigenetic markers that make them organ-specific adult stem cells ( see papers by Chia-Cheng Chang).

    Third, ln the case of human primary fibroblasts( or primary epithelial cells), spontaneous recovery of “iPS” cells does not occur…unless the early passage primary cell population, which contains a few normal organ-specific stem cells, are infected or transfected with “immortalizing viruses” or their “immortalizing genes”[ SV40; HPV]. After subsequent passages, most cells go through “crisis”, but a very few survive and are “immortal” [ but are not tumorigenic]. Most in the cancer field interpret this as the first step of carcinogenesis[ i.e. a normal somatic differentiated cell must be Immortalized or de-differentiated ( or “re-programmed)]. However, the alternative explanation is that this early passage primary culture contains a few adult organ specific stem cells ( which is normally “immormal” until it is induced to terminally differentiate or become “mortal”).. When this population is transfected with the Large T gene, the few adult immortal organ-specific stem cells , expressing p53 and RB proteins, the LT protein renders these proteins non-functional and these few adult stem cells cannot differentiate but remain “immortal”. Therefore, the first step of the multi-step, multi-mechanism of carcinogenesis is not the “immortalization” or “re-programming” of a normal “mortal” cell but the “blockage” of “mortalization” of a normal “immortal” adult organ-specific stem cell.

    Fourth, since the universally accepted definition of an “iPS”
    cell is its ability to form teratomas when injected back in vivo. Isn’t it interesting that adult human cancers formed naturally in vivo are sarcomas or carcinomas. In fact the SV40 “immortalized” cells, when injected in vivo do not form any kind of cancer ( teratomas, carcinomas or sarcomas). These “immortalized” cells need addition alterations in other oncogenes,or tumor suppressor genes[ see papers by Chia Cheng Chang]. If the first step in human carcinogenesis is the “reprogramming” or “de-differentiation” of a normal mortal or differentiated fibroblast, we should see teratomas in adult humans. However, we see sarcomas or carcinomas. All of these factual observations have been published in peer-reviewed cancer research journals for multiple decades. All these are best interpreted, using Ockham’s Razor, as supporting the stem cell hypothesis, not the “de-differentiation” or “re-programming” hypothesis of carcinogenesis.

    Fifth, since these normal “immortal” organ-specific adult stem cells also express the Oct4A gene, it should not be surprising that an exogenous addition of another Oct4 gene would give a selective advantage to this endogenously expressing Oct4A cell. Remember, it has been shown that after a few passsages, these “iPS” cells selectively shut off the exogenous Oct4A gene. But that the endogenous Oct4A remains expressed ( as well as some of the other organ-specific epigenetic markers.

    Finally, the publication of MUSE cells by the M. Dezawa group, showing that these adult stem cells, when treated with the Yamanaka factors, give rise to many more “iPS” like cells that the primary cultures.


    • Actually, the Whitehead patent names their reprogrammed cells with pluripotency as reprogrammed pluripotent somatic cell (“RPSC”), which is more candid and less controversial, compared to that Yamanaka names his reprogrammed cells with pluripotency as induced pluripotent stem cells (iPS cells), given that culture and development of iPS cells often leads to canceration or teratoma.


      • In response to:

        “Actually, the Whitehead patent names their reprogrammed cells with pluripotency as reprogrammed pluripotent somatic cell (“RPSC”), which is more candid and less controversial, compared to that Yamanaka names his reprogrammed cells with pluripotency as induced pluripotent stem cells (iPS cells), given that culture and development of iPS cells often leads to canceration or teratoma.”

        Larry:

        I agree the term “RPSC” is more candid. However, they still do not agree that the RPSC cells might have originated from organ-specific adult stem cells.

        Are you aware of any published paper where either iPS or RPSC cells, when tested in vivo, give rise to any carcinomas or sarcomas, rather than just teratomas?


    • Detail the response yourself with the following experiment.

      Make MEFS from a wild type mouse, with no exogenously introduced reprogramming factors, just wild type mice.

      Culture half the MEFs in DMEM/10%FCS.

      Culture the other half in ES cell media plus lif and 2i.

      wait 3-4 weeks report back, report back how many AP, Nanog, SSEA1 positive colonies you find.

      🙂

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