PT  - JOURNAL ARTICLE
AU  - Samuel J I Blackford
AU  - Soon Seng Ng
AU  - Joe M Segal
AU  - Aileen J F King
AU  - Jennifer Moore
AU  - Michael Sheldon
AU  - Dusko Ilic
AU  - Anil Dhawan
AU  - Ragai Mitry
AU  - S Tamir Rashid
TI  - Validation of a library of cGMP-compliant human pluripotent stem cell lines for use in liver therapy
AID  - 10.1101/298760
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 298760
4099  - http://biorxiv.org/content/early/2018/04/10/298760.short
4100  - http://biorxiv.org/content/early/2018/04/10/298760.full
AB  - 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 PEG-DA fabricated inverted colloid crystal (ICC) scaffold converted these immature progenitors into more advanced hepatic tissue structures. Hepatic constructs could also be successfully encapsulated into the immune-privileged material alginate. 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.Author ContributionsSamuel J I Blackford: Concept and design, Collection and/or assembly of data, data analysis and interpretation, manuscript writingSoon Seng Ng: Concept and design, Collection and/or assembly of data, data analysis and interpretation, manuscript writingJoe M Segal: Collection and/or assembly of dataAileen J F King: Collection and/or assembly of dataJennifer Moore: Provision of study material or patientsMichael Sheldon: Provision of study material or patientsDusko Ilic: Provision of study material or patientsAnil Dhawan: Concept and design, manuscript writingRagai Mitry: Concept and design, Collection and/or assembly of data, manuscript writingS. Tamir Rashid: Concept and design, financial support, manuscript writing, Final approval of manuscriptSJIB is supported by a GSTT BRC PhD awardSTR is supported by an MRC Clinician Scientist Award (MGSBACR)