Stem Cells Transl Med. 2015 Mar;4(3):217-23. doi: 10.5966/sctm.2014-0233. Epub 2015 Feb 3.

Enabling consistency in pluripotent stem cell-derived products for research and development and clinical applications through material standards.

French A¹, Bravery C², Smith J³, Chandra A⁴, Archibald P⁴, Gold JD⁵, Artzi N⁶, Kim HW⁷, Barker RW³, Meissner A⁸, Wu JC⁹, Knowles JC¹⁰, Williams D⁴, García-Cardeña G¹¹, Sipp D¹², Oh S¹³, Loring JF¹⁴, Rao MS¹⁵, Reeve B¹⁶, Wall I¹⁷, Carr AJ¹⁸, Bure K¹⁹, Stacey G²⁰, Karp JM²¹, Snyder EY²², Brindley DA²³.

Author information

1: 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.
2: Consulting on Advanced Biologicals Ltd., London, United Kingdom;
3: Oxford-UCL Centre for the Advancement of Sustainable Medical Innovation and.
4: Centre for Biological Engineering, Wolfson School of Mechanical and Manufacturing Engineering, Loughborough University, Loughborough, United Kingdom;
5: Stanford Cardiovascular Institute.
6: Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA;
7: Department of Dental Biomaterials, School of Dentistry.
8: 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;
9: Stanford Cardiovascular Institute, Department of Medicine, and Department of Radiology, Stanford University School of Medicine, Stanford, California, USA;
10: Department of Nanobiomedical Science BK21 Plus NBM Global Research Center of Regenerative Medicine, and Division of Biomaterials and Tissue Engineering, UCL Eastman Dental Institute.
11: 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;
12: RIKEN Center for Developmental Biology, Kobe, Japan;
13: Bioprocessing Technology Institute, A*STAR Agency for Science, Technology and Research, Singapore;
14: Department of Chemical Physiology and Center for Regenerative Medicine, Scripps Research Institute, La Jolla, California, USA;
15: NIH Center for Regenerative Medicine, Bethesda, Maryland, USA;
16: Harvard Stem Cell Institute, Cambridge, Massachusetts;
17: 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;
18: Oxford-UCL Centre for the Advancement of Sustainable Medical Innovation and Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Nuffield Orthopaedic Centre, and.
19: TAP Biosystems, Royston, United Kingdom;
20: National Institute for Biological Standards and Control, a Centre of the MHRA, South Mimms, United Kingdom;
21: 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;
22: 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.
23: 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.

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.

©AlphaMed Press.