title: Good manufacturing practice and clinical-grade human embryonic stem cell lines.
abstract: Human embryonic stem cell (hESC) lines, after directed differentiation, hold the greatest potential for cell transplantation treatment in many severe diseases. Good manufacturing practice (GMP) quality, defined by both the European Medicines Agency and the Food and Drug Administration, is a requirement for clinical-grade cells, offering optimal defined quality and safety in cell transplantation. Using animal substance-free culture media, feeder cells or feeder-free matrix in derivation, passaging, expansion and cryopreservation procedures, immune reactions against animal proteins in the cells, and infection risk caused by animal microbes can be avoided. It is also possible to apply GMP to animal components if no better options are available. In recent production of GMP-quality hESC lines, feeder cells had been cultured in fetal bovine serum, and the medium supplemented with an animal protein containing a serum replacement component. Using embryos cultured in a GMP laboratory, isolating the inner cell mass mechanically, deriving lines on human feeder cells originally cultured in xeno-free medium in a GMP laboratory, and using xeno-free media for derivation and culture of hESC lines themselves, GMP-quality xeno-free hESC lines could be established today. Human serum is a xeno-free component available today, but many chemically defined media are under development.
authors.affiliation: Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, SE-14186 Stockholm, Sweden.
authors.forename: Christian
authors.initials: C
authors.lastname: Unger
authors.forename: Heli
authors.initials: H
authors.lastname: Skottman
authors.forename: Pontus
authors.initials: P
authors.lastname: Blomberg
authors.forename: M Sirac
authors.initials: MS
authors.lastname: Dilber
authors.forename: Outi
authors.initials: O
authors.lastname: Hovatta
mesh_terms: D018929:Cell Culture Techniques / Q000379:methods / Q000592:standards*; D002460:Cell Line; D002469:Cell Separation / Q000379:methods / Q000592:standards*; D064987:Cell- and Tissue-Based Therapy; D002478:Cells, Cultured; D015925:Cryopreservation; D003470:Culture Media / Q000737:chemistry; D053595:Embryonic Stem Cells / Q000166:cytology*; D006801:Humans
chemical_list: D003470:Culture Media