Negative effects of a high tumour necrosis factor-α concentration on human gingival mesenchymal stem cell trophism: the use of natural compounds as modulatory agents

Stem Cell Research & Therapy

Alessandra Braca¹  Simona Daniele¹  Claudia Martini¹  Marinella De Leo¹  Barbara Costa¹  Chiara Giacomelli¹  M. Letizia Trincavelli¹  Letizia Natali¹  Marco Nisi²  Filippo Graziani²  Mario Gabriele² 

[1] Department of Pharmacy, University of Pisa;Department of Surgical, Medical, Molecular and Critical Area Pathology, University of Pisa;

关键词: Human gingival mesenchymal stem cells;    Tumour necrosis factor-alpha;    Endothelial cells;    Cytokine release;    Ribes nigrum;   

DOI  :  10.1186/s13287-018-0880-7

来源: DOAJ

【 摘 要 】

Abstract Background Adult mesenchymal stem cells (MSCs) play a crucial role in the maintenance of tissue homeostasis and in regenerative processes. Among the different MSC types, the gingiva-derived mesenchymal stem cells (GMSCs) have arisen as a promising tool to promote the repair of damaged tissues secreting trophic mediators that affect different types of cells involved in regenerative processes. Tumour necrosis factor (TNF)-α is one of the key mediators of inflammation that could affect tissue regenerative processes and modify the MSC properties in in-vitro applications. To date, no data have been reported on the effects of TNF-α on GMSC trophic activities and how its modulation with anti-inflammatory agents from natural sources could modulate the GMSC properties. Methods GMSCs were isolated and characterized from healthy subjects. The effects of TNF-α were evaluated on GMSCs and on the well-being of endothelial cells. The secretion of cytokines was measured and related to the modification of GMSC-endothelial cell communication using a conditioned-medium method. The ability to modify the inflammatory response was evaluated in the presence of Ribes nigrum bud extract (RBE). Results TNF-α differently affected GMSC proliferation and the expression of inflammatory-related proteins (interleukin (IL)-6, IL-10, transforming growth factor (TGF)-β, and cyclooxygenase (COX)-2) dependent on its concentration. A high TNF-α concentration decreased the GMSC viability and impaired the positive cross-talk between GMSCs and endothelial cells, probably by enhancing the amount of pro-inflammatory cytokines in the GMSC secretome. RBE restored the beneficial effects of GMSCs on endothelial viability and motility under inflammatory conditions. Conclusions A high TNF-α concentration decreased the well-being of GMSCs, modifying their trophic activities and decreasing endothelial cell healing. These data highlight the importance of controlling TNF-α concentrations to maintain the trophic activity of GMSCs. Furthermore, the use of natural anti-inflammatory agents restored the regenerative properties of GMSCs on endothelial cells, opening the way to the use and development of natural extracts in wound healing, periodontal regeneration, and tissue-engineering applications that use MSCs.

【 授权许可】

Unknown