Validation of Current Good Manufacturing Practice Compliant Human Pluripotent Stem Cell-Derived Hepatocytes for Cell-Based Therapy.
Bioengineering
Cell transplantation
Cellular therapy
Hepatocyte differentiation
Hepatocytes
Liver therapy
Pluripotent stem cells
cGMP
hESC
iPSC
Journal
Stem cells translational medicine
ISSN: 2157-6564
Titre abrégé: Stem Cells Transl Med
Pays: England
ID NLM: 101578022
Informations de publication
Date de publication:
02 2019
02 2019
Historique:
received:
10
04
2018
revised:
22
08
2018
accepted:
25
09
2018
pubmed:
21
11
2018
medline:
9
4
2020
entrez:
21
11
2018
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 30456803
doi: 10.1002/sctm.18-0084
pmc: PMC6344902
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
124-137Subventions
Organisme : Medical Research Council
ID : MR/L006537/1
Pays : United Kingdom
Organisme : NIMH NIH HHS
ID : U24 MH068457
Pays : United States
Organisme : NINDS NIH HHS
ID : U24 NS095914
Pays : United States
Informations de copyright
© 2018 The Authors. Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.
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