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Jan 15, 2012 (Vol. 32, No. 2)

Cell Culture Media Market Maturing

  • Alternative Media

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    Trends in stem cell culture media have moved toward defined varieties such as Life Technologies’ StemPro MSC SFM, which is free of animal products and cleared by the FDA for use in clinical trials.

    The “final frontier” for revolutionary media development may lie in markets other than traditional mammalian cell culture-based manufacturing, particularly in stem cells and media for “non-traditional” expression systems.

    Numerous vendors offer media for stem cell cultures.

    Through its Chemicon business unit Millipore sells HEScGRO™ animal component-free media for human embryonic stem cells; Stemgent’s NutriStem™ media is fully defined and animal component-free; Life Technologies sells several types under the Gibco brand, including StemPro® for neural stem cells, as does Aruna Biomedical with its AB2™ Neural Progenitor Expansion media Kit. Through its Hyclone brand Thermo Scientific sells a range of products for both human embryonic and adult stem cells.

    One tends to think of stem cell media as being radically different from conventional cell culture media, but this is not the case. Stem cell media consists of conventional cell nutrients such as lipids, vitamins, minerals, and amino acids, plus a proprietary blend of cytokines and co-factors that favor expansion or differentiation.

    “I don’t know that there are specific differences between media used for mesenchymal stem cells or for other mesenchymal cells,” explains Jim Musick, Ph.D., president of Vitro Diagnostics. “Media requirements depend more on the cell’s origin—mesenchymal, endodermal, epidermal—than whether it’s a stem cell or not.”

    If anything, stem cell culture media are evolving toward greater simplicity—a recapitulation of media/feed strategies for biopharmaceutical manufacturing. A paper in the May 2011 issue of Nature Methods by James Thomson at the University of Wisconsin describes a stem cell culture medium, E8, that has been stripped of all unnecessary components.

    Chemically defined E8 medium reduces variability in human embryonic and induced pluripotent stem cell cultures resulting from inconsistencies in albumin. E8 contains no albumin at all, and was pared of other ingredients that Thomson and co-workers deemed to be unnecessary.

    Thomson found that albumin was required to reduce the toxicity to cells of mercaptoethanol, so he omitted this ingredient and found that albumin was no longer required.

    David Welch, Ph.D., senior market development manager at Life Technologies, describes such media as “lean” media—both cost-effective and efficient at maintaining stem cells in whatever state of potency is desired.

    Early on, Dr. Welch explains, stem cell researchers “threw everything they could think of” into media formulations in an attempt to maintain cells in a multipotent or pluripotent state. “But as the push toward chemically defined media progressed, these investigators struggled with finding a carrier to replace BSA or human albumin."

  • Algal Cell Culture Media

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    These hanging photobioreactor bags (100 liters each) contain either red algae (Porphyridium) or green algae (Scenedesmus) used in the production of algae biofuels. [San Diego Center for Algae Biotechnology, UCSD]

    Alternative expression systems remain the Rodney Dangerfields of biomanufacturing, yet they continue to generate interest.

    A 2010 paper in Plant Biology Journal reported that algal cell culture can compete with bacterial and mammalian cell cultures for the production of therapeutic proteins. The authors, among them Stephen Mayfield at the University of California, San Diego, and scientists from Hayward, CA-based protein-engineering firm ProtElix, demonstrated the feasibility of producing a variety of therapeutic proteins, including cytokines, VEGF, and antibodies in inexpensive algal cultures.

    Algal cultures are much more robust than mammalian cell culture and, unlike bacteria, produce properly folded, glycosylated proteins. Most salient: In the paper, Mayfield noted that algae were “considerably cheaper” than mammalian expression systems.

    As with stock CHO cell culture media, end-users prefer “take out” to home cooked. Algal media is simple, consisting mostly of salts and minerals. (Being plants, algae employ carbon dioxide as their carbon source.) “As we spoke with customers, we heard that making up algal media is a pain,” says Lisa Stillwell, product development manager at Life Technologies, which claims to be the “first to market” for algal media under the Gibco brand.

    These products, Stillwell notes, are “significantly less complex” than CHO media. Some provide little more than minerals and elements—no vitamins, amino acids, or undefined components like hydrolysates or animal sera, although some algae require acetate as the carbon source for optimal growth.

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