Abstract

Mesenchymal stem cells (MSCs) are known to play a key role in tissue regeneration, while smoking cigarettes is described to impair it. This work focuses on the effect cigarette smoke extract (CSE) has on the migration, differentiation, and paracrine potential of human adipose derived MSCs (AdMSCs). To mimic native conditions in vitro, AdMSCs were cultured in either monolayer or three-dimensional pellet cultures. While constant exposure to high concentrations of CSE had lethal effects on AdMSCs, lower concentrations of CSE impaired cell migration when compared to control conditions. The secretion of key interleukins was downregulated when CSE was exposed to the cells at low concentrations. Moreover, in this work AdMSCs were exposed to CSE while simultaneously being induced to differentiate into adipocytes, osteoblasts, and chondrocytes to determine the effect of CSE on the cells potential to differentiate. While adipogenic differentiation showed no significant variation, AdMSCs exposed to osteogenic and chondrogenic supplements showed both early and late genetic level variation when acutely exposed to low concentrations of CSE. Our results indicate that even a small amount of cigarette smoke can have detrimental effects on the regenerative potential of MSCs.

Highlights

  • Trophic mediators, releasing pro-angiogenic, chemotactic, and immune modulatory factors, which play an important role in wound healing, bone and cartilage remodelling, and overall tissue regeneration[19,20]

  • The work presented here examines the effects of cigarette smoke extract (CSE) as a whole and addresses the question of how it affects the regenerative potential of adipose derived MSCs (AdMSCs) via their migration, differentiation by means of genetic expression, and paracrine potential

  • In order to study cell migration, scratch assays were used where a defined line was created between two confluent areas of AdMSCs using a chamber method (Fig. 1)

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Summary

Introduction

Trophic mediators, releasing pro-angiogenic, chemotactic, and immune modulatory factors, which play an important role in wound healing, bone and cartilage remodelling, and overall tissue regeneration[19,20]. The work presented here examines the effects of cigarette smoke extract (CSE) as a whole and addresses the question of how it affects the regenerative potential of adipose derived MSCs (AdMSCs) via their migration, differentiation by means of genetic expression, and paracrine potential. We analysed the migration and cell viability under different concentrations of CSE to test the effects of the oxidizing agents and radicals in CS21. We examined the damaging effects of CS on the release of bioactive factors from MSCs, which could in turn compromise healing and signalling for cell differentiation

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