title: Standardization of Good Manufacturing Practice-compliant production of bone marrow-derived human mesenchymal stromal cells for immunotherapeutic applications.
abstract: OBJECTIVE
  Human mesenchymal stem or stromal cells (MSCs) represent a potential resource not only for regenerative medicine but also for immunomodulatory cell therapies. The application of different MSC culture protocols has significantly hampered the comparability of experimental and clinical data from different laboratories and has posed a major obstacle for multicenter clinical trials. Manufacturing of cell products for clinical application in the European Community must be conducted in compliance with Good Manufacturing Practice and requires a manufacturing license. In Germany, the Paul-Ehrlich-Institut as the Federal Authority for Vaccines and Biomedicines is critically involved in the approval process.
  
  
  METHODS
  This report summarizes a consensus meeting between researchers, clinicians and regulatory experts on standard quality requirements for MSC production.
  
  
  RESULTS
  The strategy for quality control testing depends on the product's cell composition, the manufacturing process and the indication and target patient population. Important quality criteria in this sense are, among others, the immunophenotype of the cells, composition of the culture medium and the risk for malignant transformation, as well as aging and the immunosuppressive potential of the manufactured MSCs.
  
  
  CONCLUSIONS
  This position paper intends to provide relevant information to interested parties regarding these criteria to foster the development of scientifically valid and harmonized quality standards and to support approval of MSC-based investigational medicinal products.
authors.affiliation: Department of Medicine V, Heidelberg University, Heidelberg, Germany. Electronic address: patrick.wuchter@med.uni-heidelberg.de.
authors.forename: Patrick
authors.initials: P
authors.lastname: Wuchter
authors.affiliation: Institute of Transfusion Medicine and Immunology Mannheim, Medical Faculty Mannheim, Heidelberg University, German Red Cross Blood Donor Service Baden-Württemberg-Hessen, Mannheim, Germany.
authors.forename: Karen
authors.initials: K
authors.lastname: Bieback
authors.affiliation: Institute for Clinical Transfusion Medicine and Immunogenetics Ulm, Red Cross Blood Transfusion Service Baden-Württemberg-Hessen and University of Ulm, Ulm, Germany.
authors.forename: Hubert
authors.initials: H
authors.lastname: Schrezenmeier
authors.affiliation: Department of Internal Medicine I, University Hospital Carl Gustav Carus, Dresden, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Bornhäuser
authors.affiliation: Department of Medicine IV, University Hospital Halle (Saale), Halle (Saale), Germany.
authors.forename: Lutz P
authors.initials: LP
authors.lastname: Müller
authors.affiliation: Institute for Transfusion Medicine and Immunohematology, Goethe University, Frankfurt/Main and German Red Cross Blood Service Baden-Württemberg-Hessen, Frankfurt/Main, Germany.
authors.forename: Halvard
authors.initials: H
authors.lastname: Bönig
authors.affiliation: Helmholtz Institute for Biomedical Technology, Stem Cell Biology and Cellular Engineering, University of Aachen Medical School, Aachen, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wagner
authors.affiliation: Division of Pediatric Stem Cell Therapy, Clinic for Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Meisel
authors.affiliation: Stem Cell Laboratory, IKTZ Heidelberg GmbH, Heidelberg, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Pavel
authors.affiliation: Institute of Transfusion Medicine, Red Cross Blood Transfusion Service Dresden, Dresden, Germany.
authors.forename: Torsten
authors.initials: T
authors.lastname: Tonn
authors.affiliation: Department of Pediatrics, University Clinic Tübingen, Tübingen, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Lang
authors.affiliation: Clinic for Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Ingo
authors.initials: I
authors.lastname: Müller
authors.affiliation: Paul-Ehrlich-Institut, Federal Institute for Vaccines and Biomedicines, Langen, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Renner
authors.affiliation: Department of Medicine V, Heidelberg University, Heidelberg, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Malcherek
authors.affiliation: Department of Medicine V, Heidelberg University, Heidelberg, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Saffrich
authors.affiliation: Department of Medicine V, Heidelberg University, Heidelberg, Germany.
authors.forename: Eike C
authors.initials: EC
authors.lastname: Buss
authors.affiliation: Department of Medicine V, Heidelberg University, Heidelberg, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Horn
authors.affiliation: Institute for Clinical Transfusion Medicine and Immunogenetics Ulm, Red Cross Blood Transfusion Service Baden-Württemberg-Hessen and University of Ulm, Ulm, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Rojewski
authors.affiliation: Department of Medicine V, Heidelberg University, Heidelberg, Germany.
authors.forename: Anita
authors.initials: A
authors.lastname: Schmitt
authors.affiliation: Department of Medicine V, Heidelberg University, Heidelberg, Germany.
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Ho
authors.affiliation: Paul-Ehrlich-Institut, Federal Institute for Vaccines and Biomedicines, Langen, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Sanzenbacher
authors.affiliation: Department of Medicine V, Heidelberg University, Heidelberg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Schmitt
mesh_terms: D001853:Bone Marrow; D018929:Cell Culture Techniques / Q000592:standards; D003470:Culture Media; D005858:Germany; D019983:Guideline Adherence; D006801:Humans; D016130:Immunophenotyping; D016219:Immunotherapy, Adoptive / Q000379:methods*; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D011786:Quality Control; D044968:Regenerative Medicine / Q000379:methods
chemical_list: D003470:Culture Media
keywords: Good Manufacturing Practice; cell-based therapy; manufacturing license; mesenchymal stromal cells; standardization