title: Good manufacturing practice-grade production of unrestricted somatic stem cell from fresh cord blood.
abstract: OBJECTIVE
  The discovery of unrestricted somatic stem cells (USSC), a non-hematopoietic stem cell population, brought cord blood (CB) to the attention of regenerative medicine for defining more protocols for non-hematopoietic indications. We demonstrate that a reliable and reproducible method for good manufacturing practice (GMP)-conforming generation of USSC is possible that fulfils safety requirements as well as criteria for clinical applications, such as adherence of strict regulations on cell isolation and expansion.
  
  
  METHODS
  In order to maintain GMP conformity, the automated cell processing system Sepax (Biosafe) was implemented for mononucleated cell (MNC) separation from fresh CB. After USSC generation, clinical-scale expansion was achieved by multi-layered CellSTACKs (Costar/Corning). Infectious disease markers, pyrogen and endotoxin levels, immunophenotype, potency, genetic stability and sterility of the cell product were evaluated.
  
  
  RESULTS
  The MNC isolation and cell cultivation methods used led to safe and reproducible GMP-conforming USSC production while maintaining somatic stem cell character.
  
  
  CONCLUSIONS
  Together with implemented in-process controls guaranteeing contamination-free products with adult stem cell character, USSC produced as suggested here may serve as a universal allogeneic stem cell source for future cell treatment and clinical settings.
authors.affiliation: Institute for Transplantation Diagnostics and Cell Therapeutics, University of Duesseldorf Medical School, Germany.
authors.forename: Murat
authors.initials: M
authors.lastname: Aktas
authors.forename: Anja
authors.initials: A
authors.lastname: Buchheiser
authors.forename: Amelie
authors.initials: A
authors.lastname: Houben
authors.forename: Verena
authors.initials: V
authors.lastname: Reimann
authors.forename: Teja
authors.initials: T
authors.lastname: Radke
authors.forename: Kathrin
authors.initials: K
authors.lastname: Jeltsch
authors.forename: Patrick
authors.initials: P
authors.lastname: Maier
authors.forename: W Jens
authors.initials: WJ
authors.lastname: Zeller
authors.forename: Gesine
authors.initials: G
authors.lastname: Kogler
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D018929:Cell Culture Techniques; D019070:Cell Lineage; D002478:Cells, Cultured; D002499:Centrifugation, Density Gradient / Q000295:instrumentation / Q000379:methods; D005312:Fetal Blood / Q000166:cytology*; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D051379:Mice; D008819:Mice, Nude; D012038:Regeneration / Q000502:physiology; D033581:Stem Cell Transplantation / Q000331:legislation & jurisprudence / Q000379:methods / Q000592:standards; D013234:Stem Cells / Q000166:cytology / Q000502:physiology; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous
chemical_list: D015415:Biomarkers