• Defining a stem cell product – working proposal and recommendations
    Last 2 months I was discussing a possible definition of “stem cell product“. I polled professionals and had few opinions exchange via email and LinkedIn. Today, I’m going to summarize this discussion and propose a working definition and recommendations. Why do we need to define it? 93% of polled professionals think that it is important issue to discuss. 7% think that there is no point to do it. Unfortunately, both sides did not elaborate publicly – why they think so. […]
  • Cells Weekly – July 27, 2014

    by Alexey Bersenev on July 28, 2014 · 0 comments

    in notes

    Cells Weekly is a digest of the most interesting news and events in stem cell research, cell therapy and regenerative medicine. Cells Weekly is posted every Sunday night!


    1. “California stem cell scandal”
    We mentioned some issues with conflicts of interests in California stem cell agency – CIRM, related to departure of its former CEO Alan Trounson and company StemCells Inc. This week, some reporters dug deeper in these issues and called it not less than a “scandal”. Michael Hiltzik of LA Times (largest circulation newspaper in California) wrote:

    The agency, known formally as the California Institute for Regenerative Medicine, or CIRM, continues to demonstrate the drawbacks of its insular, insider-like way of doing business.

    The unanswered question burning a hole through CIRM’s credibility is whether Stem Cells Inc. got its money because its research was promising, or because it knew the right people.
    For most of its existence, CIRM has been deeply hostile to outside scrutiny. The harvest is now coming in.

    Blogger David Jensen continues to give more and more details about ongoing “CIRM scandal” – read his latest posts here, here, here and here.

    2. Glial origin of mesenchymal stem cells
    New study, published in Nature, demonstrates on tooth development model that mesenchymal stem cells could be originated from neural glial cells:

    Here we show that a significant population of mesenchymal stem cells during development, self-renewal and repair of a tooth are derived from peripheral nerve-associated glia.

    Using the same methodology, it will be interesting to look at origin of mesenchymal stem cells in other tissues, such as bone marrow and fat.

    3. Hematopoietic cell therapy for type 1 diabetes – results of clinical trial
    Long-term results of controlled Chinese trial, assessing autologous hematopoietic cells in children with type 1 diabetes, were published this week:

    In order to eliminate the honeymoon effect, we performed final follow-up at the 3–5 years ((4.2±1.8) years) after AHST treatment, and found that HbA1c in the control group was still lower than that in the case group (P <0.01); however, the insulin dosage and serum C-peptide were not significantly different between the two groups (P >0.05). Moreover, the insulin dosage was not significant different from baseline to follow-up period in the case group.

    Even though, few patients showed some benefit (lowering insulin dose and its withdrawal) at 6-12 months after therapy, long-term results showed no benefit:

    AHST treatment showed no advantage in effectiveness in children with newly diagnosed type 1 diabetes, both in insulin dose and long term blood glucose control.

    4. Business of Regenerative Medicine – annual course summary
    Annual business course for regenerative medicine/ cell therapy professionals finished last week in Toronto. I was following it by tweets from CCRM. Mark Curtis wrote great follow-up post this week. I’d highly recommend you to read it!

    Reimbursement is everything. While accelerated approval will get RM developers to approval, ultimately they will need to demonstrate value to the patient and cost-effectiveness to payers. Without this, easing of regulatory burdens will do little to improve global health.

    Also read post by Lee Buckler – Lessons from Toronto on the Future of Regenerative Medicine in Japan.

    5. Overview of T-cell therapies
    GEN posted a nice overview of T-cell-based technologies for immunocellular therapies in oncology:

    The idea has intrigued researchers for at least a couple of decades: Open a new front against cancer by enhancing the tumor-fighting abilities of T cells. Only recently, however, has the idea seemed anywhere near realization.

    Recommended for brief introduction to the topic.

    6. News about mitochondria transfer IVF procedure in UK
    Two interesting new came up from UK this week about controversial technique of mitochondria transfer IVF (3-parent baby). First, the Guardian gave an update on regulation and potential approval of technique:

    The Department of Health announced plans on Tuesday to press ahead with regulations following a three-month public consultation which drew 1,850 responses. The draft regulations are due to go to parliament for debate in the autumn, and could be law by April next year.

    Second, the Independent wrote on criticism of misusing term “genetically modified babies” by Government:

    Lord Winston and other scientists accuse the Government of acting by stealth as the Department of Health buries redefinition of ‘genetically modified babies’ in treatment of mitochondrial donation.

    David King, from the pressure group Human Genetics Alert, said the Government is “playing PR games based on very dubious science” because any changes to the mitochondrial genes will amount to genetic modification. “Their restriction of the term to nuclear inheritable changes is clearly political. They don’t want people like me saying that they are legalising GM babies,” Dr King said.


    Self-renewal assay for T-cells

    by Alexey Bersenev on July 26, 2014 · 0 comments

    in hematopoietic,methods

    Some subsets of memory T-cells (Tcm) were described as “stem cell-like” or “T memory stem cells“. They have all characteristics of adult stem cells, however, their self-renewal potential was tested only on population level. New study, published in Immunity, for the first time provides evidence for self-renewal of single Tcm. The authors did fantastic job in carrying out self-renewal serial transplantation assay. Luca Gattinoni in his commentary “Memory T cells officially join the stem cell club” wrote:

    It was an extraordinary undertaking, performing a serial trigenerational single-cell transfer, an experiment that was never attempted before for any type of mammalian stem cells.

    For donor cell tracking, the authors used congenic mouse model, which is very common in hematopoietic stem cell assessment. For recipient conditioning and testing functionality of donor-derived T-cells, bacterial pathogen (Listeria) was used. Single donor Tcm were sorted from mice and serially transferred into recipients for 3 rounds. Single CD62L+ Tcm fully reconstituted phenotypic diversity of T-cell lineage and provided pathogen-specific protection in this clonogenic in vivo assay.

    This study solidifies the evidence for “stemness” of Tcm and sets a “new standard” for assessment of T-cell self-renewal in vivo. Importantly, Graef described a “therapeutically ideal” subset of CD62L+ T-cells for targeting infectious pathogens and cancer.


    Methods and Protocols Digest – July, 2014

    by Alexey Bersenev on July 24, 2014 · 0 comments

    in methods,protocols

    Methods and Protocols Digest is a collection of links to the methodological articles, freely available online. Please share your protocol with community!


    Direct reprogramming skin fibroblasts of diabetic patients in insulin+ clusters (PLoS ONE)
    Direct reprogramming of mouse fibroblasts to neuronal cells (Sci World J)

    Mesenchymal Stromal Cells
    Characterization of 4 different populations of human MSCs (Int J Mol Med)
    Clonal analysis of human CD271+ MSCs (Hematologica)
    Method for 3D expansion of human bone marrow MSC (PLoS ONE)

    Pluripotent stem cells
    Human ES cell-derived insulin+ cells in diabetes model (PLoS ONE)
    Depletion of residual pluripotent cells in iPS differentiation culture by inhibition of DNA topoisomerase II (Stem Cells Dev)
    Generation of cardiomyocytes from pluripotent stem cells in suspended microcarrier cultures (Stem Cell Res)
    Robust enrichment of cardiomyocytes derived from human pluripotent stem cells (Stem Cell Reports)
    Generation of oligodendrocytes from multiple sclerosis patients by iPS (Stem Cell Reports)

    Endothelial cells
    Generation of endothelial cells from peripheral blood (J Cell Mol Med)


    20 bioprinting companies to watch

    by Alexey Bersenev on July 23, 2014 · 0 comments

    in notes

    Bioprinting is a new buzz word in biomedicine. With creation of new 3D printers and increased interest from investors, the field is starting to gain momentum and commercialize. But if you look at bioprinting as a business, all you will see is news about Organovo. But, in the last few years many new bioprinting companies are popped up. In this post I’ll highlight 20 most notable companies, developing bioprinting products.

    1. Cyfuse Biomedical
    Japanese company, founded in 2010. Makes bioprinter Regenova. Working on bioprinting few organs and tissues for drug discovery and regenerative medicine.

    2. TeVido Biodevices
    US-based private start-up company, founded in 2011. The company is working on printing breast tissue with nipples and cellular wound cover, created from patient’s adipose stem cells. Learn more from this video.

    3. Regenovo Biotechnology
    Chinese company, founded in 2013. Commercializing bioprinter “Regenovo” for “making biomaterials, organs and tissues” for regenerative medicine.

    4. Aspect Biosystems
    Private Canadian company, founded in 2013. Commercializing bioprinted “living human tissues on demand” – for Pharma R&D.

    5. Rainbow Biosciences
    A division of US public company Rainbow Coral Corp. Since 2012, the company has a joint venture and commercializing product, developed by nano 3D Biosciences – 3D BiO Assay. This assays is claimed as “the first commercially available 3D bioprinting system for drug screen”. The technology behind – magnetic levitation.

    6. RegenHU
    Private Swiss company, founded in 2007. Has few bioprinting products on a market – printer BioFactory and matrix BioInk.

    7. Osteopore International
    Clinical stage company from Singapore. Printing matrices for bone regeneration. Has 2 products on a market – Osteoplug and Osteomesh. For matrix fabrication company uses QuickSlice software offered by Stratasys Inc.

    8. Bio 3D Technologies
    Private Singaporean company, founded in 2013. Makes bioprinter – Life-Printer “X” for Pharma R&D and potential RegenMed applications.

    9. GeSiM
    German company, which makes equipment for liquid handling automation and microfluidics platforms. The company makes and sells bioprinter BioScaffolder 2.1 for printing of scaffolds in tissue engineering.

    10. Tissue Regeneration Systems
    Private US company, founded in 2008. The company “fabricate skeletal reconstruction implants”. Last year, FDA cleared the first bioprinted implant for bone regeneration as 501k device.

    11. nScrypt Inc
    US company, founded in 2002. Recently nScrypt is commercializing products for tissue bioprinting – Computer Aided Machining equipment and biomaterials.

    12. OxSyBio
    U of Oxford spin-out, founded in 2014. Company will develop bioprinted materials for wound healing and drug delivery. Read more.

    13. Next 21
    Japanese company, which provides a service for printing of custom bone implants. The company filed application for approval of bioprinter.

    15. DigiLab Inc
    US company, which makes variety of devices for life sciences. The recent product CellJet – automated live cell printer for research applications.

    16. Advanced Solutions Life Sciences
    A division of Advanced Solutions, dedicated to development software and hardware for 3D printing of tissues. Commercializing two products – Tissue Structure Information Modeling (TSIM) and BioAssemblyBot.

    17. MicroFab Technologies Inc
    US company, which offers commercial printing platform JetLab. The platform could include custom TissueJet bioprinter for tissue engineering.

    18. EnvisionTEC
    International 3D printing industry giant. A big part of company now dedicated to biofabrication. Company makes and sells printer 3D-Bioplotter for applications in tissue engineering.

    19. Seraph Robotics
    Private US company, founded in 2011. Company makes and sells 3D printing platform (hardware and sofware) Fab@Home Model 3. This platform successfully used in academic institutions to print scaffolds for tissue engineering.

    20. Organovo
    Public American company – the icon of bioprinting business. Makes printer Novogen MMX and provide tissues (NovoTissues) for R&D.


    Cells Weekly – July 20, 2014

    by Alexey Bersenev July 20, 2014 notes

    Cells Weekly is a digest of the most interesting news and events in stem cell research, cell therapy and regenerative medicine. Cells Weekly is posted every Sunday night! 1. Criticism of “cord blood for autism” trial Criticism of recently launched autism trial at Duke U is keep coming. SFARI posted a big piece about this trial, citing stem cell scientist Arnold Kriegstein: “It’s probably premature to run large trials without evidence that they have a therapeutic effect that [we] understand,” […]

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    Aneuploidy threshold for safety of MSC-based products

    by Alexey Bersenev July 19, 2014 mesenchymal

    I’ve written about aneuploidy as phenomenon, associated with expansion of mesenchymal stromal cells (MSC) and some other types of cells. Even though, aneuploidy is chromosomal abnormality, it is not necessarily associated with malignant transformation. It could “represent” senescence. The big question is how can we ensure safety of MSC-based clinical products with detected aneuploidy or other chromosomal abnormalities? Recently, a group of researchers from S. Korea, proposes to set a cut-off value for aneuploidy in clinical MSC cultures. They analyzed […]

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    Impact of controlled-rate freezing interruption on cell viability

    by Alexey Bersenev July 16, 2014 clinical lab

    If you process cells for clinical use, you probably perform cryopreservation in the device, called controlled-rate freezer (CRF). This is the most frequent and routine procedure in cord blood banking. CRF uses liquid nitrogen (LN) to cool cells in controlled manner. The whole procedure takes usually 40-60 min and finished by freezing cells at -80C. However, sometimes such freezing procedure could be interrupted by errors (the most frequent cause – not enough LN or pressure in the tank, connected to […]

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    Cells Weekly – July 13, 2014

    by Alexey Bersenev July 14, 2014 notes

    Cells Weekly is a digest of the most interesting news and events in stem cell research, cell therapy and regenerative medicine. Cells Weekly is posted every Sunday night! 1. “Stem cell therapy” complicated by excessive tissue growth 8 years later Clinical case, described by Clare Wilson in New Scientist made a biggest buzz this week. A woman received autologous olfactory mucosal cell implantation for experimental treatment of spinal cord injury. Intervention was useless and 8 years later she developed back […]

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    Breaking down fat: Considerations for adipose tissue processing

    by Alexey Bersenev July 12, 2014 adipose

    Quality and therapeutic potency of stromal vascular fraction (SVF) is very much depending on processing of adipose tissue. Cell composition of SVF can vary dramatically between different methods of processing. Unlike SVF, adipose-derived stem cells (ASC) in culture could be more homogenous. Different adipose tissue isolation techniques could affect a gene expression profile of ASC. In this post, I’ll summarize some considerations in choosing the method of fat tissue processing for further SVF or ASC isolation. Fat tissue harvesting procedure. […]

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    Six reasons to work in academic cell manufacturing facility

    by Alexey Bersenev July 8, 2014 RegenMed digest

    Cell therapy field is booming and continue to offer new jobs. Many of you looking for new positions and facing a choice between industry and academia. Today, I’d like to highlight some key differences and advantages of working in academic cell manufacturing facility as compared to industry. These career tips based on my own experience. I hope, it will help to navigate you in career choice. Possibility to participate in many different clinical trials. Usually, cell therapy academic facilities support […]

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