Chemically Defined Conditions Mediate an Efficient Induction of Dental Pulp Pluripotent-Like Stem Cells into Hepatocyte-Like Cells

Carlos Gil-Recio; Sheyla Montori; Saddam Al Demour; Mera A Ababneh; Eduard Ferrés-Padró; Carles Marti; Elvira Ferrés-Amat; Miguel Barajas; Ashraf Al Madhoun; Maher Atari

doi:10.1155/2021/5212852

Chemically Defined Conditions Mediate an Efficient Induction of Dental Pulp Pluripotent-Like Stem Cells into Hepatocyte-Like Cells

Stem Cells Int. 2021 Nov 8:2021:5212852. doi: 10.1155/2021/5212852. eCollection 2021.

Authors

Affiliations

¹ Regenerative Medicine Research Institute, UIC Barcelona, Barcelona, Spain.
² Department of Special Surgery/Division of Urology, The University of Jordan, School of Medicine, Amman, Jordan.
³ Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, Amman, Jordan.
⁴ Oral and Maxillofacial Surgery Department, Fundació Hospital de Nens de Barcelona, Barcelona, Spain.
⁵ Oral and Maxillofacial Surgery Department, Hospital Clinico de Barcelona, Barcelona, Spain.
⁶ Pediatric Dentistry Service, Oral and Maxillofacial Surgery Service, Hospital de Nens de Barcelona, Barcelona, Spain.
⁷ Biochemistry and Molecular Biology Department, Universidad Pública de Navarra, Pamplona, Spain.
⁸ Department of Genetics and Bioinformatics, Functional Genomic Unit, Dasman Diabetes Institute, Kuwait.
⁹ Biointelligent Technology Systems SL, Diputaccion 316, 3D, 08009 Barcelona, Spain.

Abstract

Liver diseases are major causes of morbidity and mortality. Dental pulp pluripotent-like stem cells (DPPSCs) are of a considerable promise in tissue engineering and regenerative medicine as a new source of tissue-specific cells; therefore, this study is aimed at demonstrating their ability to generate functional hepatocyte-like cells in vitro. Cells were differentiated on a collagen scaffold in serum-free media supplemented with growth factors and cytokines to recapitulate liver development. At day 5, the differentiated DPPSC cells expressed the endodermal markers FOXA1 and FOXA2. Then, the cells were derived into the hepatic lineage generating hepatocyte-like cells. In addition to the associated morphological changes, the cells expressed the hepatic genes HNF6 and AFP. The terminally differentiated hepatocyte-like cells expressed the liver functional proteins albumin and CYP3A4. In this study, we report an efficient serum-free protocol to differentiate DPPSCs into functional hepatocyte-like cells. Our approach promotes the use of DPPSCs as a new source of adult stem cells for prospective use in liver regenerative medicine.