Clinical grade production of mesenchymal stem cells.

Mesenchymal Stem Cells (MSCs) are multipotent adult stem cells having an immunosuppressive effect. These characteristics lead to an increasing use of MSC in graft process or for regenerative medicine. For the clinical uses of MSCs, standards are needed. The clinical grade production necessitates adhering to good manufacturing practices (GMP) to insure the delivery of a "cell drug" that is safe, reproducible and efficient. All parts of the process must be defined: the starting material (tissue origin, separation or enrichment procedures), cell density in culture, and medium (fetal calf serum (FCS) or human serum, cytokines with serum-free medium for target). But to reach the GMP goal, cells have to be cultured in as close to a closed system as possible. Analytical methods are needed to assay the active compound and impurities. At a minimum, quality control (QC) of cells must consider the phenotype, functional potential, microbiological safety, and ensure the cultured cells remain untransformed. Finally, quality assurance system (QA) procedures specific to the production of MSCs as a cell drug must be determined and implemented.