Ibuprofen in Therapeutic Concentrations Affects the Secretion of Human Bone Marrow Mesenchymal Stromal Cells, but Not Their Proliferative and Migratory Capacity.

Agnieszka Kulesza,Anna Burdzinska,Jakub Hawryluk,Leszek Paczek,Katarzyna Zielniok

doi:10.3390/biom12020287

Agnieszka Kulesza, Anna Burdzinska + Show 3 more

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https://doi.org/10.3390/biom12020287

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Journal: Biomolecules	Publication Date: Feb 10, 2022
Citations: 7	License type: CC BY 4.0

Affiliation: Medical University of Warsaw

Abstract

Mesenchymal stromal cells (MSCs) are able to modulate the immune system activity and the regeneration processes mainly through the secretion of multiple soluble factors, including prostaglandin E2 (PGE2). PGE2 is produced as a result of cyclooxygenases (COX) activity. In the present study, we investigated how ibuprofen, a nonselective COX inhibitor, affects the proliferation, migration and secretion of human bone marrow MSCs (hBM-MSCs). For this purpose, six hBM-MSCs populations were treated with ibuprofen at doses which do not differ from maximum serum concentrations during standard pharmacotherapy. Ibuprofen treatment (25 or 50 µg/mL) substantially reduced the secretion of PGE2 in all tested populations. Following ibuprofen administration, MSCs were subjected to proliferation (BrdU), transwell migration, and scratch assays, while its effect on MSCs secretome was evaluated by Proteome Profiler and Luminex immunoassays. Ibuprofen did not cause statistically significant changes in the proliferation rate and migration ability of MSCs (p > 0.05). However, ibuprofen (25 µg/mL for 3 days) significantly decreased mean secretion of: CCL2 (by 44%), HGF (by 31%), IL-6 (by 22%), VEGF (by 20%) and IL-4 (by 8%) compared to secretion of control MSCs (p < 0.05). Our results indicate that ibuprofen at therapeutic concentrations may impair the pro-regenerative properties of hBM-MSCs.

Highlights

Mesenchymal stromal cells (MSCs) are currently one of the most extensively studied mammalian cell populations [1]
The analysis revealed that both concentrations of ibuprofen caused inhibition of prostaglandin E2 (PGE2) secretion in a dose-dependent manner in hBM-MSCs (Table 2)
There were only six factors with increased secretion: Growth/Differentiation Factor (GDF)-15 (263.3% increase compared to control), uPAR (20.2% increase), macrophage migration inhibitory factor (MIF) (20.2% increase), osteopontin (17.5% increase), sex hormone binding globulin (SHBG) (13.2% increase) and CCL5 (RANTES)

Summary

Introduction

Mesenchymal stromal cells (MSCs) are currently one of the most extensively studied mammalian cell populations [1]. The easy availability, high proliferation potential and low immunogenicity are features that make MSCs an ideal tool for regenerative medicine. From a clinical point of view, an essential property of MSCs is an ability of migration to the site of injury, allowing them to act locally in the inflamed area [2]. The detailed mechanisms of the therapeutic action of MSCs are not fully understood. It is postulated that the main regenerative potential of MSCs is related to the stimulation of endogenous regenerative mechanisms and immunomodulatory activity [8].

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