Mouse decellularised liver scaffold improves human embryonic and induced pluripotent stem cells differentiation into hepatocyte-like cells

• Published in: PloS one Vol. 12; no. 12; p. e0189586
• Main Authors: Lorvellec, Maëlle, Scottoni, Federico, Crowley, Claire, Fiadeiro, Rebeca, Maghsoudlou, Panagiotis, Pellegata, Alessandro Filippo, Mazzacuva, Francesca, Gjinovci, Asllan, Lyne, Anne-Marie, Zulini, Justine, Little, Daniel, Mosaku, Olukunbi, Kelly, Deirdre, De Coppi, Paolo, Gissen, Paul
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 20.12.2017; Public Library of Science (PLoS)
• Subjects: Animal models; Animals; Biochemistry; Biology; Biology and Life Sciences; Blood vessels; Cell culture; Cell Differentiation; Childrens health; Comparative analysis; Computer architecture; Differentiation (biology); Embryo cells; Embryonic stem cells; Embryonic Stem Cells - cytology; Endoderm; Extracellular Matrix; Fetuses; Genetic aspects; Glycogen; Hepatocytes; Hepatocytes - cytology; Hospitals; Humans; Immunosuppression; Induced Pluripotent Stem Cells - cytology; Laboratories; Liver; Liver cirrhosis; Liver diseases; Liver transplantation; Liver transplants; Medicine; Medicine and Health Sciences; Metabolism; Mice; Physiological aspects; Pluripotency; Protocol (computers); Regeneration (physiology); Regenerative medicine; Research and Analysis Methods; Stem cell transplantation; Stem cells; Tissue engineering; Tissue Scaffolds; Transplantation; Transplants & implants; Two dimensional models; α-Fetoprotein; United Kingdom
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0189586

Liver transplantation is the definitive treatment of liver failure but donor organ shortage limits its availability. Stem cells are highly expandable and have the potential to differentiate into any specialist cell. Use of patient-derived induced Pluripotent Stem Cells (hiPSCs) has the additional advantage for organ regeneration therapies by removing the need for immunosuppression. We compared hepatocyte differentiation of human embryonic stem cells (hESCs) and hiPSCs in a mouse decellularised liver scaffold (3D) with standard in vitro protocol (2D). Mouse livers were decellularised preserving micro-architecture, blood vessel network and extracellular matrix. hESCs and hiPSCs were primed towards the definitive endoderm. Cells were then seeded either in 3D or 2D cultures and the hepatocyte differentiation was continued. Both hESCs and hiPSCs differentiated more efficiently in 3D than in 2D, with higher and earlier expression of mature hepatocyte marker albumin, lipid and glycogen synthesis associated with a decrease in expression of fetal hepatocyte marker alpha-fetoprotein. Thus we conclude that stem cell hepatocyte differentiation in 3D culture promotes faster cell maturation. This finding suggests that optimised 3D protocols could allow generation of mature liver cells not achieved so far in standard 2D conditions and lead to improvement in cell models of liver disease and regenerative medicine applications.