Yilin Tu (Hannover, DE), Dr. Anna K. Szafrańska (Hannover, DE), Henning Hartwig (Hannover, DE), Taoran Qu (Hannover, DE), Dr. Szymon Piotr Szafrański (Hannover, DE), Dr. Andreas Winkel (Hannover, DE), Prof. Dr. Meike Stiesch (Hannover, DE)
Abstract text (incl. figure legends and references)
Introduction
Human dental pulp stem cells (hDPSCs) are attracting significant attention in dentistry due to their ability to differentiate into odontoblasts and osteoblasts. The physiology of hDPSCs is modulated by environmental factors, including interactions with human and microbial cells. However, these processes have not been extensively studied.
Objectives
The aim of the study was to investigate exosome-based interactions between hDPSCs and other eukaryotic cells as well as metabolic interactions between hDPSCs and oral microorganisms.
Material and Methods
The effect of conditioned cell culture medium (CM) or exosomes from diverse eukaryotic cells on mineralization and osteo-/odontogenic differentiation was evaluated using Alizarin Red S staining, immunoblotting, ELISA and alkaline phosphatase activity assay. The effects of culture supernatant or short-chain fatty acids (SCFAs) from Fusobacterium nucleatum, on hDPSCs were characterized using same methods but also CellTiter-Blue assay, CLSM and SEM. Gene expression profiling at a whole-genome level was assessed using microarrays.
Results
The differentiation and mineralization abilities of hDPSCs were significantly improved only by treatment with exosomes from HUVECs, while CM from NHOst and M2-polarised macrophages enhanced calcium deposition alone. High concentrations of SCFAs decreased cell viability and increased cell size. Treatment of hDPSCs with F. nucleatum culture supernatant or butyrate reduced mineralization. Gene expression profiling revealed an inhibition potential of butyrate regarding differentiation of hDPSCs through TGF-β/BMP signalling pathway.
Conclusion
This study demonstrated various effects of conditions modulated by both eukaryotic and bacterial cells on the physiology of hDPSCs and highlighted the importance of a specific stem cell microenvironment in the successful implementation of tissue regeneration approaches in dentistry.