• What is the correct name for “mesenchymal stem cells”? A poll
    I’d like to refresh our Mesenchymal stem cells – definition and assays series. Today I’d like to offer you a poll. For background information you can read the first two parts of the series: A brief history of the term Assay-based definition discussion Please vote and express your opinion in comments below. What is the correct name for “mesenchymal stem cells” poll direct link: http://poll.fm/3doxa All Stem Cell Assays polls

    • 10 companies to watch in 2012

    by Alexey Bersenev on January 27, 2012 · 0 comments

    in RegenMed digest

    2011 was very interesting year for cell therapy industry. We’re expecting even more exciting news this year. Today I’d like to overview some companies, which, in my opinion, could be worth watching in 2012. I’m giving a special attention to the companies:

    • with therapeutic platforms on clinical trials
    • with unique therapeutic approaches
    • with products which just entered the market

    Advanced Cell Technology (OTC:ACTC ,US)
    The whole world is eagerly watching the first results of clinical trials, involved embryonic stem cells. Advanced Cell Technology (ACT) just release a two cases report for treatment of for macular degeneration. No adverse events or complications was reported in 4-month outcome. Some signs of vision improvement has been observed. 4 patients were treated so far, including 3 in US and 1 in UK. ACT is expecting to report more interim results of its Phase 1/2 trial later this year. If ACT will succeed at this stage and will able to show long-term safety, it will shape and determine the future development and commercialization of embryonic stem cell-based products.

    Sangamo Biosciences (Nasdaq:SGMO, US)
    The company is pioneering a new sophisticated approach for treatment of HIV patients by cell gene therapy. The approach is very unique and involves targeting the chemokine molecule CCR5 in patient’s T-cells by ZNFs. The company recently reported data from Phase 1 trial. Sangamo initiated two new Phase 2 HIV clinical trials ahead the schedule. So, this year we’re expecting to see interim results of HIV Phase 2, as well as results of other trials conducting by Sangamo. I think, it’s very promising approach in gene therapy, which eventually will enter the market.

    ImmunoCellular Therapeutics (OTC:IMUC, US)
    IMUC is developing a immunocellular therapy for treatment of glioblastoma. This is the only cell therapy in clinical trial phase, which precisely target cancer stem cells. The preliminary results of Phase 2, reported in 2011, were very compelling. The company is expecting to present interim results of Phase 2 (expanded to 21 centers) at the end of the year. Many professionals have a high expectations about Phase 2 trial.

    Human Stem Cell Institute (MICEX:ISKJ, Russia)
    HSCI just got an authorization for sales of the first gene therapy drug in Russia. It will be interesting to watch a commercialization of gene therapy on regional market. How much could it make in profit? Will physicians prescribe it? HSCI also has a cell therapy product on the market. SPRS-therapy is an autologous fibroblasts for cosmetic applications. The first approved cell therapy product in Russia brought about $0.5M USD in revenue last year (personal communication with CEO). It will be interesting to compare revenue of SPRS-therapy in Russian market and Laviv (Fibrocell) in US market.

    Dendreon (Nasdaq:DNDN, US)
    Last year we watched how the first cell cancer vaccine was feeling on the market. We saw how dramatically Dendreon’s shares fell after missed sales forecast. Nonetheless, the first cellular immunotherapeutic product on the market has generated $228M revenue in 2011. The company is optimistic about this year and forecast for $500M in 2012 sales. We will continue to watch Dendreon closely in 2012.

    Medipost (KOSDAQ:078160, S. Korea)
    Two weeks ago, Medipost got a market approval for the first allogeneic stem cell drug – Cartistem. in Korea. This approval is result of 10 years hard work, including controlled clinical trials. It will be very interesting to watch how well allogeneic “off-the-shelf” stem cell product will be doing on the regional market. Now Medipost is looking for a strategic partners abroad for international sales.

    Northwest Biotherapeutics (OTCBB:NWBO, US)
    The company is developing a dendritic cell-based cancer vaccines for more than a decade. NWBO is a main competitor for the Dendreon and IMUC on a shared market with a similar therapeutic approach. Now NWBO got very close to the point of possible approval of DCVax-Prostate for non-metastatic prostate cancer. Phase 3 trial includes more than 600 patients in multiple sites. This year, the company is expanding DCVax-L trial for glioblastoma. 240 patients in more than 25 sites will be enrolled in Phase 2 DCVax-L trial. We’re expecting to hear some interim results later this year.

    Mesoblast Limited (ASX:MSB, Australia)
    Mesoblast was one of public companies which was feeling well on the market in 2011. Company’s strong cash position allows to develop multiple products simultaneously. The recent strategic alliances with Teva and Lonza captured a lot of attention to the company. In 2012 we’re expecting to hear interim results of FDA-approved trial for type 2 diabetes and, possibly, results of other trials. Company got very close to the point of market approval.

    Osiris (Nasdaq:OSIR, US)
    Osiris is trying very hard to enter the market with a first off-the-shelf mesenchymal stem cell product in US. They had many ups and downs. Now, Osiris has finished enrollment in Phase 3 trial for GvHD. So, we’re eagerly waiting of results. If results will be positive, more likely, Prochymal will enter the market. Also, we’re expecting to hear some news from Phase 3 trial for Crohn’s disease.

    Capricor (private, US)
    This is the only private company in my review. The company with unique approach to regenerate the heart – by using cardiac progenitor cells. Only the company with women’s management team. Capricor has autologous and allogeneic Phase 2 clinical trials. The positive results of CADUCEUS and launch Phase 2 of ALLSTAR trials have captured a lot of attention to the company.

    Disclosure: I don’t own stock and I don’t have any financial interest in any company mentioned in this post.

    ***********************
    RegenMed Digest on Stem Cell Assays is sponsored by Regenerative Medicine Jobs. Please visit Regenerative Medicine Jobs for recent position openings.

    Tagged as: business, clinical trial, market, regenerative medicine, RegenMed

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    Genomic instability in human pluripotent stem cells derivatives

    by Alexey Bersenev on January 25, 2012 · 0 comments

    in embryonic/iPS

    We now know, that pluripotent (embryonic and iPS) stem cells are prone to acquisition of mutations during propagation in culture. We also know that adult stem cells can undergo spontaneous transformation. But we still don’t know about genomic stability of pluripotent stem cells derivatives – the cells which we intend to use for therapy. The recent study by Nathalie Lefort’s group, published in Journal of Clinical Investigation, shed some light on this problem. The brief summary of their findings:

    • Neural stem cells, derived from human embryonic stem (ES) cells frequently acquire genomic mutations;
    • Duplication of chromosome 1q was observed in non-random pattern regardless of genetic origin;
    • This type of mutation was specific for neural stem cell derivatives only and was not observed in original ES and iPS cells;
    • Genomic instability appeared in late passages (15-65) of neural derivatives, but not in early passages (10-22);
    • Some other types of mutations were observed;
    • These mutations gave a growth advantage in culture;
    • Mutation was associated with loss of senescence;
    • Neural stem cells carrying the mutation failed to engraft in mouse brain:

    In order to determine long-term consequences of the 1q duplication, we also implanted VUB01-NSCs carrying the defect or not into the brains of 10 adult female nude rats. At 7 weeks after transplantation, nonaffected grafted cells were recovered in all cases. In contrast, NSCs carrying the 1q duplication systematically failed to integrate and expand in the host brain.

    The authors pointed to 4 clinical trials, involved neural derivatives of human ES cells – 3 Advanced Cell Technology’s and 1 Geron’s trial. Well, eye cells are neural derivatives, can’t argue. The message of the study is a call for extreme caution for use of ES- and iPS cell-derivatives in clinical trials without monitoring of genomic stability. We should develop the assays for genomic stability of pluripotent cells derivatives as soon as possible.

    I highly recommend you to read a commentary by Neil Harrison:

    Although the chromosomal changes detected by Varela and colleagues are considered undesirable in a therapeutic setting, the inconvenient truth is that they may be inescapable, and merely demonstrate the fundamental process of natural selection. Evolutionary influences act in all living systems, with random mutation creating variants better suited to growth in a given environment. In vitro, this process has been termed culture adaptation, and it has already been reported in a number of cell types, including human ES cells.

    Regardless of the tumorigenic properties of these cells, this is an alarming observation, given that the raison d’etre for these cells is to create functional neurons.

    For those keen on taking ES cell–derived products to the clinic, the data generated by Varela and colleagues are clearly concerning.

    Well, more trouble for ES/ iPS cell-based products developers.

    Tagged as: embryonic stem cell, genomic stability, iPS, risk, safety

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    Scientists occupy publishers!

    by Alexey Bersenev on January 23, 2012 · 1 comment

    in open science

    As you know, since the first day, we are advocating and promoting open science. Today, we would call you to act. We can’t stay aside. We would like to support the movement emerging among scientists worldwide.

    The tipping point has arrived! The system of publishing in academia doesn’t function properly any more! Academic publishers have become the enemies of science! We should declare a war!

    Every scientist wants:

    • disseminate knowledge and make it easily accessible as fast as possible;
    • to see validation and reproducibility of their data in other labs around the world;
    • to make results of their research applicable and useful for society.

    The right and proper way to accomplish these goals is an open science. The new era of open science is so inevitable, why should we wait any longer?
    Open science:

    Unfortunately, academic publishers are not supporting all of these necessities any more, as it was historically. They are limiting and taking serious actions against the open science and science in general. They don’t want dissemination, exchange of knowledge and translation scientific ideas to useful technologies. How do they do it? By implementing:

    This is not a full list of academic publishers sins, which we can’t just silently observe any more. All of this about money:

    The result would be an ethical disaster: preventable deaths in developing countries, and an incalculable loss for science in the USA and worldwide. The only winners would be publishing corporations such as Elsevier (£724m profits on revenues of £2b in 2010 – an astounding 36% of revenue taken as profit).

    So, why we are willing to give our knowledge for free to corporations which sell it back to us? Nearly all scientific research done on taxpayer money. Why taxpayer should pay twice – to fund a significant research and to read the results? You know why:

    The returns are astronomical: in the past financial year, for example, Elsevier’s operating profit margin was 36% (£724m on revenues of £2bn). They result from a stranglehold on the market. Elsevier, Springer and Wiley, who have bought up many of their competitors, now publish 42% of journal articles.

    And more:

    Almost everyone is Scholarly Poor. They have no access to medical articles other than paying 40 USD per day for each one. They are denied access to life-saving knowledge for the greater good of preserving the publishing industry.

    Vote either for profit or for access to knowledge.

    Now, the important part. We can and we should do a lot about this. We should act now:

    Unfortunately, most of these actions can be taken only by faculty members, who have a voice in academia. But “scholarly young” (grad students and postdocs) also can act by spreading the information.

    Some examples and quotes of scientists who have boycotted academic publishers:
    Timothy Gowers:

    If I’m asked to referee a paper for an Elsevier journal and I am clearly an appropriate choice of referee, then refusing to do it feels like a criticism of the editor who has asked me, who may well be somebody I know. It also feels like shirking my duty and slightly letting down the authors, who may well also be people I know.

    So I am not only going to refuse to have anything to do with Elsevier journals from now on, but I am saying so publicly. I am by no means the first person to do this, but the more of us there are, the more socially acceptable it becomes, and that is my main reason for writing this post.

    Danah Boyd:

    I vow that this is the last article that I will publish to which the public cannot get access. I am boycotting locked-down journals and I’d like to ask other academics to do the same.
    Academic publishers: Wake up or get out. Silencing the voices of academics is unacceptable. You’re not helping scholarship or scholars. Find a new business model or leave the journal publishing world. You may be making money now, but your profits will not continue to grow using this current approach. Furthermore, I’d bank on academics shunning you within two generations.

    Dear scientists, it’s time to take actions and join the movement. Dear young scientists, you are the future. Let’s bring open science and make scientific information free and easily accessible! It’s time to wake up!

    Tagged as: open science

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    Lecture: David Scadden – Prospects for stem cell-based medicine

    by Alexey Bersenev on January 22, 2012 · 0 comments

    in lectures

    David Scadden is a Professor of Medicine at Harvard University and co-director of Harvard Stem Cell Institute.

    This talk was recorded at American Society for Reproductive Medicine annual meeting in October 2011. I’ve picked this talk mainly because he gives a nice historical timeline.

    2011 Plenary Session: Prospects for Stem Cell-Based Medicine from ASRM on Vimeo.

    Tagged as: HSC, lecture, Scadden D., talk

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    Cryopreservation could affect the function of mesenchymal stromal cells

    by Alexey Bersenev January 20, 2012 cell product

    The recent study by Jacques Galipeau’s group showed that immunosuppressive function of human mesemchymal stromal cells could be diminished by cryopreservation procedure: We here tested the hypothesis that the banked, cryopreserved MSC often used in clinical trials display biologic properties distinct from that of MSC in the log phase of growth typically examined in pre-clinical studies. In freshly thawed cryopreserved MSC derived from normal human volunteers, we observed that MSC up-regulate heat-shock proteins, are refractory to interferon (IFN)-γ-induced up-regulation of [...]

    Tagged as: cell product, cryopreservation, MSC, MSC assays, potency assay

    1 comment Read the full article →

    God knows what was in that vial!

    by Alexey Bersenev January 18, 2012 notes

    Exposure of ugly “stem cell tourism” is continuing. The recent journalist’s investigation of “stem cell tourism” was aired on Global News TV (Canada). I was stunned by personal story of stem cell” fraud victim Jerry Nischuk. In interview he said (min 12-13): “Mexican nurse walked down from upstairs with a little vial. God knows what was in that vial…” This is exactly the point that I was making lately – if we don’t know what was injected, we can’t call [...]

    Tagged as: business, stem cell, stem cell therapy

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    Experimental bone marrow transplantation 101 – part 5: Analysis of donor chimerism in the blood

    by Alexey Bersenev January 16, 2012 hematopoietic

    This is a part 5 of the series “Experimental bone marrow transplantation 101“. Today we will look at one of methods for detection of donor-derived cells in peripheral blood. Donor chimerism after BMT reflects engraftment of stem and progenitor cells in bone marrow (BM). The term “repopulation” is generally used to describe chimerism in the blood. The terms “chimerism” and “repopulation” frequently used as synonyms. In order to detect chimerism after BMT, donor cells should be (i) genetically different from [...]

    Tagged as: assay, BMT 101, BMT model, chimerism, competitive repopulation, engraftment, flow cytometry

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    Conditional cell immortalization using ROCK-inhibitor

    by Alexey Bersenev January 15, 2012 methods

    Maintaining the primary cells in culture sometimes is very difficult task. Some normal and malignant cells types just don’t grow well in culture. It makes very difficult cell-based diagnostics and therapy development. Recently, the group of researchers proposed the method, which allows to overcome this problem. They called it “conditional immortalization”. From Science Daily: “We tried breast cells and they grew well. We tried prostate cells and their growth was fantastic, which is amazing because it is normally impossible to [...]

    Tagged as: cell culture, immortalization, ROCK inhibitor

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    Series of retractions from Amy Wagers’ stem cell lab

    by Alexey Bersenev January 11, 2012 notes

    We wrote about some “high profile” paper retractions in stem cell field. Unfortunately, very recently, we’ve got more retractions from Amy Wagers lab at Harvard Stem Cell Institute. I think, it’s important to follow-up on this case, because her studies had a significant impact in the field. In 2010, Nature retracted Wagers paper about rejuvenation of blood stem cell niches. The whole chain reaction of events has followed later: Blood posts “notice of concern” over second Wagers-Mayack paper Editor of [...]

    Tagged as: retraction

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    Support Sabrina Cohen Foundation!

    by Alexey Bersenev January 10, 2012 notes

    I’m always amazed by enthusiasm of patient’s advocates, especially by those with tragic personal stories. Among them, the brightest advocates of stem cell research – Christopher Reeve, Roman Reed and Sabrina Cohen. Sabrina Cohen is a great supporter and advocate of stem cell research. She endured spinal cord injury from a car accident when she was a teenager. In 2006 she created Sabrina Cohen Foundation to educate a public about stem cells and raise funds for research. Up to date, [...]

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