The recent SafeCell study, published in PLoS ONE, analyzed the safety profile of mesenchymal stromal cells (MSC), administered systemically in patients. I blogged about it here. One of the most interesting things was a comparison of infusion-related toxicity between MSC, cultured in different culture conditions, particularly – with fetal bovine serum (FBS) or without. Let’s look at results.
36 randomized controlled and uncontrolled clinical studies were analyzed. 27 of the 36 studies used FBS for MSC cultures, 5 – human serum and 4 – unknown source. As we can see, vast majority (75%) of clinical cell manufacturing protocols still use FBS for culture. So, if FBS has any negative impact on toxicity we would expect acute infusion-related reactions. But, the authors concluded that was no any safety issues with MSC infusions:
No significant relationship between MSC administration and acute infusional toxicity was observed.
The only toxicity reported was a transient fever:
There was a significant association between MSC administration and the development of fever. Fever was transient and not associated with long term sequelae. The mechanisms for fever are not clear but could be related to acute inflammatory reactions by a subset of patients to particular preparations of MSCs, not unlike similar reactions occasionally observed with red blood cell administration.
The use of FBS in cell therapy products manufacturing was highly criticized. But, as this study demonstrates, transition to xeno-free protocols seem to be slow. The authors discussed “serum issue”:
Although the majority of included studies used fetal bovine serum, only one study specifically monitored for potential adverse events associated with its use. Concerns over fetal bovine serum will likely decrease in the future as expansion of MSCs in human blood products becomes more commonplace.
So, despite a big “xeno-free” movement, many clinical sites still use FBS for MSC culture. Although, there is no evidence for increased toxicity after used of FBS in MSC culture, we need studies, which will address this issue specifically.
If you have any experience with use of FBS for clinical MSC culture, please share it in comments. We would like to hear any observations from “serum versus no serum” procedures.