Open AccessValidation of Current Good Manufacturing Practice Compliant Human Pluripotent Stem Cell‐Derived Hepatocytes for Cell‐Based Therapy
Author(s) -
Blackford Samuel J.I.,
Ng Soon Seng,
Segal Joe M.,
King Aileen J.F.,
Austin Amazon L.,
Kent Deniz,
Moore Jennifer,
Sheldon Michael,
Ilic Dusko,
Dhawan Anil,
Mitry Ragai R.,
Rashid S. Tamir
Publication year - 2019
Publication title -
stem cells translational medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.781
H-Index - 71
eISSN - 2157-6580
pISSN - 2157-6564
DOI - 10.1002/sctm.18-0084
Subject(s) - induced pluripotent stem cell , cell therapy , regenerative medicine , good manufacturing practice , stem cell , transplantation , progenitor cell , scaffold , tissue engineering , cell culture , directed differentiation , microbiology and biotechnology , hepatic stellate cell , ethylene glycol , embryonic stem cell , cancer research , biology , biomedical engineering , chemistry , medicine , pathology , biochemistry , genetics , gene , regulatory affairs , organic chemistry
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