Cigarette smoke challenges bone marrow mesenchymal stem cell capacities in guinea pig

Area of Science:

• Regenerative Medicine
• Stem Cell Biology
• Toxicology

Background:

• Cigarette smoke (CS) is linked to reduced circulating stem cells and impaired stem cell function.
• The impact of CS on bone marrow-derived mesenchymal stem cells (BM-MSCs) homing and functionality remains unclear.
• This study investigates CS effects on BM-MSC homing and function using an animal model.

Purpose of the Study:

• To evaluate the effect of cigarette smoke (CS) exposure on the homing and functional capabilities of bone marrow-derived mesenchymal stem cells (BM-MSCs).
• To assess in vivo and in vitro consequences of CS exposure on BM-MSC behavior.

Main Methods:

• Guinea pigs (GPs) were exposed to CS or sham conditions.
• BM-MSCs were administered to GPs via tracheal instillation or vascular routes.
• BM-MSCs were isolated from CS-exposed or sham-exposed GPs and analyzed for proliferation, migration, senescence, differentiation, and gene expression.

Main Results:

• CS-exposed animals exhibited greater BM-MSC lung infiltration compared to sham-exposed animals.
• BM-MSCs from CS-exposed animals showed reduced engraftment, proliferation, and migration.
• In vitro, CS extract exposure dose-dependently reduced BM-MSC proliferation, differentiation, and migration, while increasing senescence.

Conclusions:

• Short-term CS exposure induces significant BM-MSC dysfunction.
• This dysfunction affects BM-MSC homing and proliferation in CS-exposed lungs and impairs their function in vitro.
• CS exposure reduces CXCL9 gene expression in bone marrow, suggesting a potential mechanism for BM dysfunction.