title: International Society for Cellular Therapy perspective on immune functional assays for mesenchymal stromal cells as potency release criterion for advanced phase clinical trials.
abstract: Mesenchymal stromal cells (MSCs) as a pharmaceutical for ailments characterized by pathogenic autoimmune, alloimmune and inflammatory processes now cover the spectrum of early- to late-phase clinical trials in both industry and academic sponsored studies. There is a broad consensus that despite different tissue sourcing and varied culture expansion protocols, human MSC-like cell products likely share fundamental mechanisms of action mediating their anti-inflammatory and tissue repair functionalities. Identification of functional markers of potency and reduction to practice of standardized, easily deployable methods of measurements of such would benefit the field. This would satisfy both mechanistic research as well as development of release potency assays to meet Regulatory Authority requirements for conduct of advanced clinical studies and their eventual registration. In response to this unmet need, the International Society for Cellular Therapy (ISCT) addressed the issue at an international workshop in May 2015 as part of the 21st ISCT annual meeting in Las Vegas. The scope of the workshop was focused on discussing potency assays germane to immunomodulation by MSC-like products in clinical indications targeting immune disorders. We here provide consensus perspective arising from this forum. We propose that focused analysis of selected MSC markers robustly deployed by in vitro licensing and metricized with a matrix of assays should be responsive to requirements from Regulatory Authorities. Workshop participants identified three preferred analytic methods that could inform a matrix assay approach: quantitative RNA analysis of selected gene products; flow cytometry analysis of functionally relevant surface markers and protein-based assay of secretome. We also advocate that potency assays acceptable to the Regulatory Authorities be rendered publicly accessible in an "open-access" manner, such as through publication or database collection.
authors.affiliation: Department of Hematology and Medical Oncology, Winship Cancer Institute, and Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA. Electronic address: jgalipe@emory.edu.
authors.forename: Jacques
authors.initials: J
authors.lastname: Galipeau
authors.affiliation: Section of Hematology, Stem Cell Research Laboratory and Cell Factory, Department of Medicine, University of Verona, Verona, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Krampera
authors.affiliation: Stem Cell Allotransplantation Section, Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: John
authors.initials: J
authors.lastname: Barrett
authors.affiliation: Regenerative and Heamatological Medicine, King's College London, London, UK.
authors.forename: Francesco
authors.initials: F
authors.lastname: Dazzi
authors.affiliation: Regenerative Medicine, Athersys Inc., Cleveland, OH, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Deans
authors.affiliation: School of Engineering and Materials Science, Queen Mary University of London, London, UK.
authors.forename: Joost
authors.initials: J
authors.lastname: DeBruijn
authors.affiliation: Department of Medical and Surgical Sciences for Children and Adults, Division of Oncology, University-Hospital of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Dominici
authors.affiliation: Department of Immunohematology and Bloodtransfusion, Leiden University Medical Centre, Leiden, Netherlands.
authors.forename: Willem E
authors.initials: WE
authors.lastname: Fibbe
authors.affiliation: Center for Cell and Gene Therapy, Baylor College of Medicine, Houston Methodist Hospital, Texas Children's Hospital, Houston, TX, USA.
authors.forename: Adrian P
authors.initials: AP
authors.lastname: Gee
authors.affiliation: Center for Stem Cell Research and Regenerative Medicine, Department of Medicine, and Department of Surgery, Tulane University School of Medicine, New Orleans, LA, USA.
authors.forename: Jeffery M
authors.initials: JM
authors.lastname: Gimble
authors.affiliation: Department of Medicine, University of Wisconsin-Madison, School of Medicine and Public Health, and University of Wisconsin Carbone Cancer Center, Madison, WI, USA.
authors.forename: Peiman
authors.initials: P
authors.lastname: Hematti
authors.affiliation: Department of Haematology, St George's Hospital and Medical School, London, UK; Blood Services Group, Health Sciences Authority, Singapore.
authors.forename: Mickey B C
authors.initials: MB
authors.lastname: Koh
authors.affiliation: Division of Clinical Immunology and Transfusion Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Katarina
authors.initials: K
authors.lastname: LeBlanc
authors.affiliation: Department of Biomedicine, University Hospital Basel, Basel, Switzerland.
authors.forename: Ivan
authors.initials: I
authors.lastname: Martin
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Ian K
authors.initials: IK
authors.lastname: McNiece
authors.affiliation: Mesoblast Inc., New York, NY, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Mendicino
authors.affiliation: Stem Cell Group, Bioprocessing Technology Institute, Agency for Science Technology and Research (A*STAR), Singapore.
authors.forename: Steve
authors.initials: S
authors.lastname: Oh
authors.affiliation: Division of Occupational and Environmental Health Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Luis
authors.initials: L
authors.lastname: Ortiz
authors.affiliation: Department of Molecular Therapeutics, The Scripps Research Institute, Jupiter, FL, USA.
authors.forename: Donald G
authors.initials: DG
authors.lastname: Phinney
authors.affiliation: IFR150 STROMALab UMR 5273 UPS-CNRS-EFS-INSERM U1031, Toulouse, France.
authors.forename: Valerie
authors.initials: V
authors.lastname: Planat
authors.affiliation: Institute of Health Sciences, Chinese Academy of Sciences, Shanghai, China; The First Affiliated Hospital, Soochow University Institutes for Translational Medicine, Suzhou, China.
authors.forename: Yufang
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Cell Processing Section, Department of Transfusion Medicine Clinical Center, NIH, Bethesda, MD, USA.
authors.forename: David F
authors.initials: DF
authors.lastname: Stroncek
authors.affiliation: Cell Therapy Program, University Health Network, Toronto, Canada.
authors.forename: Sowmya
authors.initials: S
authors.lastname: Viswanathan
authors.affiliation: Department of Medicine, University of Vermont College of Medicine, Burlington, VT, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Weiss
authors.affiliation: UMR5273 STROMALab CNRS/EFS/UPS-INSERM U1031, Toulouse, France.
authors.forename: Luc
authors.initials: L
authors.lastname: Sensebe
mesh_terms: D001681:Biological Assay / Q000379:methods*; D015415:Biomarkers / Q000378:metabolism; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology*
chemical_list: D015415:Biomarkers
keywords: ISCT; Mesenchymal Stromal cells; clinical trials; immune functional testing; matrix assays; potency assays; release assays