Effects of Ibuprofen and Diclofenac Pre-Treatment on Viability and Apoptosis Processes in Human Dental Pulp Stem Cells
Author:
Adamičková Adriana1ORCID, Kyselovic Jan12, Adamička Matúš3, Chomaničová Nikola4, Valášková Simona4, Šalingová Barbara1, Molitorisová Miroslava4, Červenák Zdenko1, Danišovič Ľuboš3, Gažová Andrea5ORCID
Affiliation:
1. 5th Department of Internal Medicine, Faculty of Medicine, Comenius University Bratislava, Špitálska 24, 81372 Bratislava, Slovakia 2. Department of Pharmacology and Toxicology, University of Veterinary Medicine and Pharmacy, 04181 Košice, Slovakia 3. Institute of Medical Biology, Genetics and Clinical Genetics, Faculty of Medicine, Comenius University Bratislava, Špitálska 24, 81372 Bratislava, Slovakia 4. International Laser Centre, Slovak Centre of Scientific and Technical Information, Lamačská cesta 7315/8A, 84104 Bratislava, Slovakia 5. Institute of Pharmacology and Clinical Pharmacology, Faculty of Medicine, Comenius University Bratislava, Špitálska 24, 81372 Bratislava, Slovakia
Abstract
Background and Objectives: Stem cell-based regeneration strategies have shown therapeutic efficacy in various fields of regenerative medicine. These include bone healing after bone augmentation, often complicated by pain, which is managed by using nonsteroidal anti-inflammatory drugs (NSAIDs). However, information is limited about how NSAIDs affect the therapeutic potential of stem cells. Materials and Methods: We investigated the effects of ibuprofen and diclofenac on the characteristics, morphology, and immunophenotype of human mesenchymal stromal cells isolated from the dental pulp (DPSCs) and cultured in vitro, as well as their effects on the expression of angiogenic growth factors (VEGFA and HGF) and selected genes in apoptosis signalling pathways (BAX, BAK, CASP3, CASP9, and BCL2). Results: Ibuprofen and diclofenac significantly reduced the viability of DPSCs, while the expression of mesenchymal stem cell surface markers was unaffected. Both ibuprofen and diclofenac treatment significantly upregulated the expression of HGF, while the expression of VEGFA remained unchanged. Ibuprofen significantly altered the expression of several apoptosis-related genes, including the upregulation of CASP9 and BCL2, with decreased CASP3 expression. BAK, CASP3, CASP9, and BCL2 expressions were significantly increased in the diclofenac-treated DPSCs, while no difference was demonstrated in BAX expression. Conclusions: Our results suggest that concomitant use of the NSAIDs ibuprofen or diclofenac with stem cell therapy may negatively impact cell viability and alter the expression of apoptosis-related genes, affecting the efficacy of stem cell therapy.
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