Cigarette smoke challenges bone marrow mesenchymal stem cell capacities in guinea pig.
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 × 106BM-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.
Department of Pulmonary Medicine, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)-University of Barcelona, Villarroel, 170, Barcelona, 08036, Spain.|Biomedical Research Networking Center in Respiratory Diseases (CIBERES), Madrid, Spain.
Olga
O
Tura-Ceide
Department of Pulmonary Medicine, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)-University of Barcelona, Villarroel, 170, Barcelona, 08036, Spain.
Borja
B
Lobo
Department of Pulmonary Medicine, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)-University of Barcelona, Villarroel, 170, Barcelona, 08036, Spain.
Tanja
T
Paul
Department of Pulmonary Medicine, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)-University of Barcelona, Villarroel, 170, Barcelona, 08036, Spain.
Raquel
R
Puig-Pey
Department of Pulmonary Medicine, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)-University of Barcelona, Villarroel, 170, Barcelona, 08036, Spain.
Núria
N
Coll-Bonfill
Department of Pulmonary Medicine, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)-University of Barcelona, Villarroel, 170, Barcelona, 08036, Spain.
Jéssica
J
García-Lucio
Department of Pulmonary Medicine, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)-University of Barcelona, Villarroel, 170, Barcelona, 08036, Spain.
Valérie
V
Smolders
Department of Pulmonary Medicine, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)-University of Barcelona, Villarroel, 170, Barcelona, 08036, Spain.|Biomedical Research Networking Center in Respiratory Diseases (CIBERES), Madrid, Spain.
Isabel
I
Blanco
Department of Pulmonary Medicine, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)-University of Barcelona, Villarroel, 170, Barcelona, 08036, Spain.|Biomedical Research Networking Center in Respiratory Diseases (CIBERES), Madrid, Spain.
Joan A
JA
Barberà
Department of Pulmonary Medicine, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)-University of Barcelona, Villarroel, 170, Barcelona, 08036, Spain. VPEINADO@clinic.ub.es.|Biomedical Research Networking Center in Respiratory Diseases (CIBERES), Madrid, Spain. VPEINADO@clinic.ub.es.
Víctor I
VI
Peinado
D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects / Q000276:immunology* / Q000473:pathology*; D002465:Cell Movement / Q000276:immunology; D000073865:Cigarette Smoking / Q000009:adverse effects*; D006168:Guinea Pigs; D008297:Male; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000276:immunology* / Q000473:pathology*; D023421:Models, Animal; D012906:Smoke / Q000009:adverse effects*
D012906:Smoke
Cell homing-chemokines; Chronic obstructive pulmonary disease; Cigarette smoke; Mesenchymal stem cells