To the Editor:
In the letter referring to our recent review published in Human Gene Therapy (Sensebé et al., 2011), Jens Reinhardt, Albert Stühler, and Johannes Blümel addressed various questions regarding media that could be used to produce mesenchymal stem/stromal cells (MSCs). The major question concerned the use of fetal bovine serum. We reported that there are concerns regarding fetal bovine serum (FBS) for cell culture, and, perhaps not having direct information, we wrongly stated that the Paul-Ehrlich-Institut (PEI) completely banishes FBS use for MSC production; but we also wrote that “FBS can still be used for GMP production of MSCs.” Although it is true that FBS can be secured from animals originating from countries free of bovine spongiform encephalopathy (BSE), such as New Zealand at this moment, and by irradiating the serum, there are some remaining problems that should lead to a decrease in, or abandonment of, the use of FBS for the production of cells that will be used for therapeutic purposes and not for producing vaccines. When FBS is added to culture medium, xenogeneic proteins are present inside MSCs (Spees et al., 2004) and can be presented by HLA to the immune system, leading to immunization and sometimes to failure of the therapeutic procedure (Horwitz et al., 2002; Sundin et al., 2007). In fact, it is important to keep in mind that MSCs are immunosuppressive but not immunoprivileged cells. Moreover, zoonoses are still a major concern, and we cannot exclude the risk of newly emerging pathogens crossing the species barrier as proven in the past by the BSE story.
As we stated in our review, there are two main alternatives to FBS: human blood-derived products and completely defined serum-free media. Regarding safety, human blood donations are tested for blood-transmitted pathogens improving the safety of all blood derived products such as plasma, serum, or platelet lysatewell as. Moreover, these human alternatives to FBS originate from platelets and plasma donations that are or could be subjected to viral inactivation, using currently authorized processes, adding an additional step toward viral safety. In this case they are a safe alternative to FBS use. Lastly, the use of platelet lysate allows a decrease in culture time and thus the time of exposure of cells to potential external pathogens that could be present in the supplement.
As pointed out in our review and in this letter, to date there is no complete defined medium of GMP grade available, but having such a medium for MSC production should be an important goal. However, while waiting for complete defined serum-free media of GMP grade, the use of safe human blood-derived products such as platelet lysate must be considered a real alternative to FBS.
