@article{f251dee1853e4145bd29300291f05ed6,
title = "Validation of Current Good Manufacturing Practice Compliant Human Pluripotent Stem Cell-Derived Hepatocytes for Cell-Based Therapy",
abstract = "Recent advancements in the production of hepatocytes from human pluripotent stem cells (hPSC-Heps) afford tremendous possibilities for treatment of patients with liver disease. Validated current good manufacturing practice (cGMP) lines are an essential prerequisite for such applications but have only recently been established. Whether such cGMP lines are capable of hepatic differentiation is not known. To address this knowledge gap, we examined the proficiency of three recently derived cGMP lines (two hiPSC and one hESC) to differentiate into hepatocytes and their suitability for therapy. hPSC-Heps generated using a chemically defined four-step hepatic differentiation protocol uniformly demonstrated highly reproducible phenotypes and functionality. Seeding into a 3D poly(ethylene glycol)-diacrylate fabricated inverted colloid crystal scaffold converted these immature progenitors into more advanced hepatic tissue structures. Hepatic constructs could also be successfully encapsulated into the immune-privileged material alginate and remained viable as well as functional upon transplantation into immune competent mice. This is the first report we are aware of demonstrating cGMP-compliant hPSCs can generate cells with advanced hepatic function potentially suitable for future therapeutic applications. Stem Cells Translational Medicine 2019;8:124&14.",
keywords = "Bioengineering, Cell transplantation, Cellular therapy, Hepatocyte differentiation, Hepatocytes, Liver therapy, Pluripotent stem cells, cGMP, hESC, iPSC",
author = "Blackford, {Samuel J.I.} and Ng, {Soon Seng} and Segal, {Joe M.} and King, {Aileen J.F.} and Austin, {Amazon L.} and Deniz Kent and Jennifer Moore and Michael Sheldon and Dusko Ilic and Anil Dhawan and Mitry, {Ragai R.} and Rashid, {S. Tamir}",
note = "Funding Information: Generation of the GMP line LiPSC-GR1.1 was supported by the NIH Common Fund Regenerative Medicine Program, and reported in Stem Cell Reports. The NIH Common Fund and the National Center for Advancing Translational Sciences (NCATS) are joint stewards of the LiPSC-GR1.1 resource. We acknowledge Cell and Gene Therapy Catapult (London, U.K.) and Dr. Ricardo Baptista for the generation and provision of the CGT-RCiB-10 hiPSC line. We thank the Nikon Imaging Centre at Kings College London for help with spinning disk confocal microscopy. We are grateful to the KCH NHS Foundation Trust, BRC Flow Cytometry Facility for advice and technical assistance, and Dr. Nicholas Powell for provision of Rag2γ mice. S.J.I.B. was supported by a GSTT BRC Ph.D. award. S.T.R. was supported by an MRC Clinician Scientist Award (MGSBACR). Funding Information: Generation of the GMP line LiPSC-GR1.1 was supported by the NIH Common Fund Regenerative Medicine Program, and reported in Stem Cell Reports. The NIH Common Fund and the National Center for Advancing Translational Sciences (NCATS) are joint stewards of the LiPSC-GR1.1 resource. We acknowledge Cell and Gene Therapy Catapult (London, U.K.) and Dr. Ricardo Baptista for the generation and provision of the CGT-RCiB-10 hiPSC line. We thank the Nikon Imaging Centre at Kings College London for help with spinning disk confocal microscopy. We are grateful to the KCH NHS Foundation Trust, BRC Flow Cytometry Facility for advice and technical assistance, and Dr. Nicholas Powell for provision of Rag2? mice. S.J.I.B. was supported by a GSTT BRC Ph.D. award. S.T.R. was supported by an MRC Clinician Scientist Award (MGSBACR). Publisher Copyright: {\textcopyright} 2018 The Authors. Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press",
year = "2019",
month = feb,
doi = "10.1002/sctm.18-0084",
language = "English (US)",
volume = "8",
pages = "124--137",
journal = "Stem cells translational medicine",
issn = "2157-6564",
publisher = "AlphaMed Press",
number = "2",
}