The manufacture of clinical-grade cellular products often requires ex vivo culture and expansion of human cells.
Fetal bovine serum (FBS) is frequently used as a supplement to basal cell culture media during expansion; however, its use poses risks including the potential for viral and prion transmission, and the possibility of adverse immunological reactions. Consequently, regulatory bodies across the globe are advising against the continued use in cell manufacturing.
A Xeno-Free Alternative
In view of these considerations, xenogenic-free culture conditions are desirable. Among the options available to replace FBS, the human platelet lysate PLUS™ Cell Culture Supplement has become the superior choice. It is a rich, cell-free supplement produced from human donor plateletpheresis products that contains a broad spectrum of growth factors, including platelet-derived growth factor (PDGF), epithelial growth factor (EGF), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), hepatocyte growth factor (HGF), and transforming growth factor β1 (TGF-β1), that support cell adhesion, growth, and proliferation.
Commercial Scale Reliability
Traditionally, similar products have been prepared by individual laboratories in small batches using protocols that differ in the number of platelet units pooled, the processing of platelets, and the requirement for heparin. These small batches are typically not compliant with good manufacturing practices (GMP), which is an important consideration when translating manufacturing processes for clinical applications. Additionally, many smaller-scale providers utilize heparin to prevent fibrinogen clotting upon contact with calcium in culture medium; not only is commercially available heparin derived from porcine sources (nullifying efforts to remove all xenogeneic supplements), it does not remove fibrinogen, which has been shown to negatively affect the immunomodulatory functions of cultured stem cells. These differences can significantly impact stem cell growth, morphology, and functionality.
A solution to these issues is the use of PLUS™ which is manufactured using a highly standardized, industrial-scale production process. Each lot is produced by pooling platelet units from at least 100 donors, resulting in a product with very consistent growth factor profiles and cell culture performance. Additionally, PLUS™ is available as a GMP-grade product, providing a safe, efficacious, reproducible, and xenogeneic-free alternative to FBS. As a human-derived product, PLUS™ does not harbor the risk of xenogeneic immune reactions or infections with bovine pathogens, and the GMP-grade product is already being used in FDA-approved clinical cell therapy protocols, reducing the risk in translating research to the clinic. Prior FDA approval for use of PLUS™ in clinical trial protocols has set a precedent for future approvals for manufacturers looking to switch from FBS to a human platelet lysate.
PLUS™ has been shown to promote the efficient proliferation and migration of a range of human cell types, including bone marrow and cord blood-derived mesenchymal stromal cells (MSCs), adipose-derived MSCs (ASCs), human umbilical vein endothelial cells (HUVECs), keratinocytes, fibroblasts, and is currently being tested and optimized for use with NK cells and T-cells.
Stem cells have been shown to expand extensively in medium supplemented with PLUS™, with significantly higher yields than when cultured in FBS. When expanded over multiple passages, stem cells of multiple derivations have also been shown to maintain their spindle morphology, expression of characteristic surface markers, and are more easily detached from plastic with trypsin. Stem cells cultured with PLUS™ maintain their differentiation ability. The immunosuppressive activity is comparable between PLUS™ and FBS-expanded hMSCs/hASCs due to PLUS™’s minimal fibrinogen concentration.
The higher proliferation rates and lower doubling times seen with PLUS™ imply a greater cell yield compared to FBS. These higher cell yields translate into more cost and time savings for manufacturers. Using PLUS™ throughout the entire cell manufacturing process, from isolation of cells, to ex vivo expansion, and cryopreservation can reduce overall costs, when compared to using FBS.
Compass Biomedical’s technical support team is able to assist you with your research protocol transitions, production scale-up and clinical regulatory support to help you make the switch from FBS to PLUS™.