Researchers at King’s College London have submitted the first animal-free, clinical grade, human embryonic stem cell (hES) line to the UK Stem Cell Bank. The hES line is the result of almost ten years of work and will be freely available to the research community. These cells are being hailed as the gold standard for future stem cell clinical research and treatments because the line is considered “clinical grade.” Up to this point, hES lines have been only “research grade,” and while some of these lines are in clinical trials now, they have been granted approval for only limited studies and for a limited time. Research grade cell lines are not appropriate for long-term study or suitable for widespread human therapies.

Companies like Pfizer and Advanced Cell Technology are currently using research grade human embryonic stem cells that have been approved for human clinical studies after they have demonstrated that all animal products have been removed from the cells. Research grade cells are only given a temporary designation of clinical grade for the duration of a specific study, typically short safety studies. It is clear that these cells are not appropriate for expanded clinical studies or human treatment and to qualify these cells for such a purpose would require extensive additional testing. The clinical grade cell lines from King’s College London have been grown completely free of any animal products, which eliminates the need to perform extensive testing to ensure that all animal products have been removed.

Stem cells are frequently grown using animal components, including fetal bovine serum, and there is always a concern about adventitious infectious agents contaminating the stem cells. Animal-derived cell culture products have been known to carry viruses and prions (including bovine spongiform encephalopathy the causative agent in mad cow disease), which contaminate cells and could compromise the safety of the patient. Due to safety concerns, animal components have been largely removed from biopharmaceutical manufacturing, but they still are prevalent in stem cell processes.

While additional testing still needs to be conducted at the UK Stem Cell Bank, it is estimated that the clinical grade cells would be available for clinical studies by 2014. Researcher Professor Peter Braude of King’s College London, UK stated in a recent article in BioNews, “We had to get to the point where everything we’re using is animal free, or in some way has been tested to be safe or its provenance known – you can’t have something that has been exposed to pig, mouse or cow injected into humans. The ‘holy grail’ is where you start the [cell] line from the point where it is clean enough to be used for clinical therapy – all the ingredients are clean.”

This is a very exciting development for the future of stem cell therapies. The elimination of animal products does improve safety and reduce the risk of contamination, but what about human derived products? When stem cells are not grown using animal components, they are frequently grown using human derived ingredients, including human serum albumin and human transferrin. Human derived ingredients are also cause for concern as they may contain adventitious infectious agents despite the testing done on human blood. In a previous blog titled, “Cell Therapy and the use of Plasma Derived Ingredients,” it was discussed how Factor VIII, at the time a protein derived from blood, was used to treat many hemophiliacs. Before the discovery of HIV and Hepatitis C, this treatment tragically resulted in many hemophiliacs becoming infected. At the time we simply did not know what to look for when testing donated blood. Now Factor VIII is produced as a recombinant protein, thus eliminating the safety concerns about treating patients with blood products. Since we don’t know if there will be another HIV type virus and we can’t say that all known infectious agents are detected with 100 percent accuracy, we can’t say that human-derived products are completely safe for culturing stem cells.

Is this new gold standard the best we can do? There is no question that this is an important development and that animal-free cell lines are the best option currently available, but shouldn’t we aim for cells to be grown free of animal and human derived products. With the new recombinant products available like recombinant albumin, recombinant transferrin, and several other recombinant growth factors, it seems we can achieve a completely animal and human product free stem cell line and culture system.

Is anyone working in this area? If so, please tell us about your experience removing animal and human derived products from stem cell culture.

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