title: Enabling consistency in pluripotent stem cell-derived products for research and development and clinical applications through material standards.
abstract: There is a need for physical standards (reference materials) to ensure both reproducibility and consistency in the production of somatic cell types from human pluripotent stem cell (hPSC) sources. We have outlined the need for reference materials (RMs) in relation to the unique properties and concerns surrounding hPSC-derived products and suggest in-house approaches to RM generation relevant to basic research, drug screening, and therapeutic applications. hPSCs have an unparalleled potential as a source of somatic cells for drug screening, disease modeling, and therapeutic application. Undefined variation and product variability after differentiation to the lineage or cell type of interest impede efficient translation and can obscure the evaluation of clinical safety and efficacy. Moreover, in the absence of a consistent population, data generated from in vitro studies could be unreliable and irreproducible. Efforts to devise approaches and tools that facilitate improved consistency of hPSC-derived products, both as development tools and therapeutic products, will aid translation. Standards exist in both written and physical form; however, because many unknown factors persist in the field, premature written standards could inhibit rather than promote innovation and translation. We focused on the derivation of physical standard RMs. We outline the need for RMs and assess the approaches to in-house RM generation for hPSC-derived products, a critical tool for the analysis and control of product variation that can be applied by researchers and developers. We then explore potential routes for the generation of RMs, including both cellular and noncellular materials and novel methods that might provide valuable tools to measure and account for variation. Multiparametric techniques to identify "signatures" for therapeutically relevant cell types, such as neurons and cardiomyocytes that can be derived from hPSCs, would be of significant utility, although physical RMs will be required for clinical purposes.
authors: Oxford-UCL Centre for the Advancement of Sustainable Medical Innovation and anna.french@casmi.org.uk david.brindley@ndorms.ox.ac.uk esnyder@sanfordburnham.org.
authors: Anna
authors: A
authors: French
authors: Consulting on Advanced Biologicals Ltd., London, United Kingdom;
authors: Christopher
authors: C
authors: Bravery
authors: Oxford-UCL Centre for the Advancement of Sustainable Medical Innovation and.
authors: James
authors: J
authors: Smith
authors: Centre for Biological Engineering, Wolfson School of Mechanical and Manufacturing Engineering, Loughborough University, Loughborough, United Kingdom;
authors: Amit
authors: A
authors: Chandra
authors: Centre for Biological Engineering, Wolfson School of Mechanical and Manufacturing Engineering, Loughborough University, Loughborough, United Kingdom;
authors: Peter
authors: P
authors: Archibald
authors: Stanford Cardiovascular Institute.
authors: Joseph D
authors: JD
authors: Gold
authors: Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA;
authors: Natalie
authors: N
authors: Artzi
authors: Department of Dental Biomaterials, School of Dentistry.
authors: Hae-Won
authors: HW
authors: Kim
authors: Oxford-UCL Centre for the Advancement of Sustainable Medical Innovation and.
authors: Richard W
authors: RW
authors: Barker
authors: Harvard Stem Cell Institute, Cambridge, Massachusetts; Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts, USA;
authors: Alexander
authors: A
authors: Meissner
authors: Stanford Cardiovascular Institute, Department of Medicine, and Department of Radiology, Stanford University School of Medicine, Stanford, California, USA;
authors: Joseph C
authors: JC
authors: Wu
authors: Department of Nanobiomedical Science BK21 Plus NBM Global Research Center of Regenerative Medicine, and Division of Biomaterials and Tissue Engineering, UCL Eastman Dental Institute.
authors: Jonathan C
authors: JC
authors: Knowles
authors: Centre for Biological Engineering, Wolfson School of Mechanical and Manufacturing Engineering, Loughborough University, Loughborough, United Kingdom;
authors: David
authors: D
authors: Williams
authors: Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA; Center for Excellence in Vascular Biology, Department of Pathology, and Program in Developmental and Regenerative Biology, Harvard Medical School, Boston, Massachusetts, USA;
authors: Guillermo
authors: G
authors: García-Cardeña
authors: RIKEN Center for Developmental Biology, Kobe, Japan;
authors: Doug
authors: D
authors: Sipp
authors: Bioprocessing Technology Institute, A*STAR Agency for Science, Technology and Research, Singapore;
authors: Steve
authors: S
authors: Oh
authors: Department of Chemical Physiology and Center for Regenerative Medicine, Scripps Research Institute, La Jolla, California, USA;
authors: Jeanne F
authors: JF
authors: Loring
authors: NIH Center for Regenerative Medicine, Bethesda, Maryland, USA;
authors: Mahendra S
authors: MS
authors: Rao
authors: Harvard Stem Cell Institute, Cambridge, Massachusetts;
authors: Brock
authors: B
authors: Reeve
authors: Oxford-UCL Centre for the Advancement of Sustainable Medical Innovation and Department of Nanobiomedical Science BK21 Plus NBM Global Research Center of Regenerative Medicine, and Department of Biochemical Engineering, and Biomaterials and Tissue Engineering Laboratory, Department of Nanobiomedical Science and WCU Research Center, Dankook University, Cheonan, Republic of Korea;
authors: Ivan
authors: I
authors: Wall
authors: Oxford-UCL Centre for the Advancement of Sustainable Medical Innovation and Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Nuffield Orthopaedic Centre, and.
authors: Andrew J
authors: AJ
authors: Carr
authors: TAP Biosystems, Royston, United Kingdom;
authors: Kim
authors: K
authors: Bure
authors: National Institute for Biological Standards and Control, a Centre of the MHRA, South Mimms, United Kingdom;
authors: Glyn
authors: G
authors: Stacey
authors: Harvard Stem Cell Institute, Cambridge, Massachusetts; Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA; Center for Regenerative Therapeutics and Department of Medicine, Division of Biomedical Engineering, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA;
authors: Jeffrey M
authors: JM
authors: Karp
authors: Sanford-Burnham Medical Research Institute, La Jolla, California, USA; Department of Pediatrics, School of Medicine, University of California, San Diego, La Jolla, California, USA; Sanford Consortium for Regenerative Medicine, La Jolla, California, USA; anna.french@casmi.org.uk david.brindley@ndorms.ox.ac.uk esnyder@sanfordburnham.org.
authors: Evan Y
authors: EY
authors: Snyder
authors: Oxford-UCL Centre for the Advancement of Sustainable Medical Innovation and Harvard Stem Cell Institute, Cambridge, Massachusetts; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts, USA; Saïd Business School, University of Oxford, Oxford, United Kingdom; Centre for Behavioural Medicine, UCL School of Pharmacy, University College London, London, United Kingdom; Stanford-UCSF FDA Center of Excellence in Regulatory Science and Innovation (CERSI), San Francisco, California, USA anna.french@casmi.org.uk david.brindley@ndorms.ox.ac.uk esnyder@sanfordburnham.org.
authors: David A
authors: DA
authors: Brindley
mesh_terms: D035843:Biomedical Research / Q000295:instrumentation / Q000379:methods / Q000592:standards / Q000639:trends; D004353:Drug Evaluation, Preclinical / Q000191:economics / Q000379:methods / Q000592:standards / Q000639:trends; D006801:Humans; D039904:Pluripotent Stem Cells; D012015:Reference Standards
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