Ascorbic Acid/Retinol and/or Inflammatory Stimuli’s Effect on Proliferation/Differentiation Properties and Transcriptomics of Gingival Stem/Progenitor Cells
Karim M. Fawzy El-Sayed,
Amira Bittner,
Kristina Schlicht,
Mohamed Mekhemar,
Kim Enthammer,
Marc Höppner,
Martha Es-Souni,
Juliane Schulz,
Matthias Laudes,
Christian Graetz,
Christof E. Dörfer,
Dominik M. Schulte
Affiliations
Karim M. Fawzy El-Sayed
Clinic for Conservative Dentistry and Periodontology, School of Dental Medicine, Christian-Albrechts-University of Kiel, 24105 Kiel, Germany
Amira Bittner
Clinic for Conservative Dentistry and Periodontology, School of Dental Medicine, Christian-Albrechts-University of Kiel, 24105 Kiel, Germany
Kristina Schlicht
Institute of Diabetes and Clinical Metabolic Research, School of Medicine, Christian-Albrechts-University of Kiel, 24104 Kiel, Germany
Mohamed Mekhemar
Clinic for Conservative Dentistry and Periodontology, School of Dental Medicine, Christian-Albrechts-University of Kiel, 24105 Kiel, Germany
Kim Enthammer
Institute of Diabetes and Clinical Metabolic Research, School of Medicine, Christian-Albrechts-University of Kiel, 24104 Kiel, Germany
Marc Höppner
Institute of Clinical Molecular Biology, School of Medicine, Christian-Albrechts-University of Kiel, 24105 Kiel, Germany
Martha Es-Souni
Department of Orthodontics, School of Dental Medicine, University Clinic Schleswig-Holstein (UKSH), Christian-Albrechts University of Kiel, 24105 Kiel, Germany
Juliane Schulz
Institute of Diabetes and Clinical Metabolic Research, School of Medicine, Christian-Albrechts-University of Kiel, 24104 Kiel, Germany
Matthias Laudes
Institute of Diabetes and Clinical Metabolic Research, School of Medicine, Christian-Albrechts-University of Kiel, 24104 Kiel, Germany
Christian Graetz
Clinic for Conservative Dentistry and Periodontology, School of Dental Medicine, Christian-Albrechts-University of Kiel, 24105 Kiel, Germany
Christof E. Dörfer
Clinic for Conservative Dentistry and Periodontology, School of Dental Medicine, Christian-Albrechts-University of Kiel, 24105 Kiel, Germany
Dominik M. Schulte
Institute of Diabetes and Clinical Metabolic Research, School of Medicine, Christian-Albrechts-University of Kiel, 24104 Kiel, Germany
The present study explored the effects of ascorbic-acid (AA)/retinol and timed inflammation on the stemness, the regenerative potential, and the transcriptomics profile of gingival mesenchymal stem/progenitor cells’ (G-MSCs). STRO-1 (mesenchymal stem cell marker) immuno-magnetically sorted G-MSCs were cultured in basic medium (control group), in basic medium with IL-1β (1 ng/mL), TNF-α (10 ng/mL) and IFN-γ (100 ng/mL, inflammatory-medium), in basic medium with AA (250 µmol/L) and retinol (20 µmol/L) (AA/retinol group) or in inflammatory medium with AA/retinol (inflammatory/AA/retinol group; n = 5/group). The intracellular levels of phosphorylated and total β-Catenin at 1 h, the expression of stemness genes over 7 days, the number of colony-forming units (CFUs) as well as the cellular proliferation aptitude over 14 days, and the G-MSCs’ multilineage differentiation potential were assessed. Next-generation sequencing was undertaken to elaborate on up-/downregulated genes and altered intracellular pathways. G-MSCs demonstrated all mesenchymal stem/progenitor cells characteristics. Controlled inflammation with AA/retinol significantly elevated NANOG (p p p FOS, EGR1, SGK1, CXCL5, SIPA1L2, TFPI2, KRATP1-5), survival (EGR1, SGK1, TMEM132A), differentiation and mineral absorption (FOS, EGR1, MT1E, KRTAP1-5, ASNS, PSAT1), inflammation and MHC-II antigen processing (PER1, CTSS, CD74) and intracellular pathway activation (FKBP5, ZNF404). Less as well as more genes were activated the longer the G-MSCs remained in the inflammatory medium or AA/retinol, respectively. Combined, current results point at possibly interesting interactions between controlled inflammation or AA/retinol affecting stemness, proliferation, and differentiation attributes of G-MSCs.
