The online version of this article (doi:10.1186/s12931-017-0530-0) contains supplementary material, which is available to authorized users.
Cigarette smoke (CS) is associated with lower numbers of circulating stem cells and might severely affect their mobilization, trafficking and homing. Our study was designed to demonstrate in an animal model of CS exposure whether CS affects the homing and functional capabilities of bone marrow-derived mesenchymal stem cells (BM-MSCs).
Guinea pigs (GP), exposed or sham-exposed to CS, were administered via tracheal instillation or by vascular administration with 2.5 × 106 BM-MSCs obtained from CS-exposed or sham-exposed animal donors. Twenty-four hours after cell administration, animals were sacrificed and cells were visualised into lung structures by optical microscopy. BM-MSCs from 8 healthy GP and from 8 GP exposed to CS for 1 month were isolated from the femur, cultured in vitro and assessed for their proliferation, migration, senescence, differentiation potential and chemokine gene expression profile.
CS-exposed animals showed greater BM-MSCs lung infiltration than sham-exposed animals regardless of route of administration. The majority of BM-MSCs localized in the alveolar septa. BM-MSCs obtained from CS-exposed animals showed lower ability to engraft and lower proliferation and migration. In vitro, BM-MSCs exposed to CS extract showed a significant reduction of proliferative, cellular differentiation and migratory potential and an increase in cellular senescence in a dose dependent manner.
Short-term CS exposure induces BM-MSCs dysfunction. Such dysfunction was observed in vivo, affecting the cell homing and proliferation capabilities of BM-MSCs in lungs exposed to CS and in vitro altering the rate of proliferation, senescence, differentiation and migration capacity. Additionally, CS induced a reduction in CXCL9 gene expression in the BM from CS-exposed animals underpinning a potential mechanistic action of bone marrow dysfunction.
Additional file 1: Figure S1. Caspase 3 expression in BM-MSCs after stimulation with vehicle or different concentrations of CSE: BM-MSCs were incubated 24h with increasing concentrations of CSE. The graph shows the mean and the standard deviation of the relative gene expression (left graph). MTT-kit cell viability assay (Vybrant MTT cell proliferation assay kit) in. BM-MSCs after stimulation with vehicle or after different concentrations of CSE (right graph). All experiments were done in technical and biological triplicates. A P value of higher than 0.05 was considered not statistically significant (P > 0.05). (DOCX 696 kb)
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- Cigarette smoke challenges bone marrow mesenchymal stem cell capacities in guinea pig
Joan A. Barberà
Víctor I. Peinado
- BioMed Central
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