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

Author:

Gil-Recio Carlos1,Montori Sheyla1,Al Demour Saddam2,Ababneh Mera A.3,Ferrés-Padró Eduard4,Marti Carles5,Ferrés-Amat Elvira6,Barajas Miguel7,Al Madhoun Ashraf8ORCID,Atari Maher19ORCID

Affiliation:

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.

Funder

“la Caixa” Foundation

Publisher

Hindawi Limited

Subject

Cell Biology,Molecular Biology

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