Bone marrow stem cells therapy alleviates vascular injury in a chronic obstructive pulmonary disease‑obstructive sleep apnea overlap syndrome rat model

Abstract

Chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) are highly prevalent potential risk factors for systemic disease. Previous studies have reported that COPD and OSA are major independent risk factors for cardio-or cerebrovascular diseases. The present study aimed to investigate the role of bone marrow mesenchymal stem cells (BMSCs) on vascular injury in a COPD-OSA overlap syndrome (OS) rat model. Rats were randomly divided into three groups: Sham, OS model and BMSC. BMSC localization in major organs was detected via confocal laser fluorescence microscopy, and the aortic tissue pathological changes and related genes were measured using hematoxylin & eosin and Masson staining. Genes associated with vascular endothelial cell injury, including endothelin 1, vascular cell adhesion molecule 1 and endothelial nitric oxide synthase, were detected via reverse transcription-quantitative PCR and western blotting. Apoptosis of vascular endothelial cells was detected using TUNEL and immunofluorescence assays. The endothelial cell marker CD31 in injured vessels was analyzed via immunohistochemistry. BMSCs migrated into the heart, liver, spleen, lung, kidney, brain and aorta in the OS model. The green fluorescence expression of BMSCs demonstrated the highest level in the lung, followed by the aorta. Aortic tissue had a more severe vascular injury and increased apoptosis in the model group compared with the BMSC group. Vascular endothelial cell apoptosis was decreased in the BMSC group compared with the model group. The findings suggested that BMSCs could repair vascular injury by inhibiting endothelial cell damage and apoptosis. These data provide a theoretical basis for the treatment of cardiovascular diseases caused by OS with BMSCs.

Molecular Mechanisms Responsible for Mesenchymal Stem Cell-Based Modulation of Obstructive Sleep Apnea

“…In line with these findings are results obtained by Bi et al and Chen et al who investigated therapeutic potential of MSCs in animal model of chronic obstructive pulmonary disease (COPD)-OSA overlap syndrome (OS) ( Table 1 ). They demonstrated that MSCs differentiated in functional ECs and efficiently attenuated OS-triggered vascular injury in the lungs [ 33 , 34 ]. OS was induced by exposing experimental rats to the cigarette smoke ((15 cigarettes at once, two times daily) and intermittent hypoxia (with ~99% nitrogen (N 2 ) for 30 s and air (~21% O 2 ) every day for 90 s, 30 times per hour, 8 h per day) for 8 weeks [ 33 , 34 ].…”

“…They demonstrated that MSCs differentiated in functional ECs and efficiently attenuated OS-triggered vascular injury in the lungs [ 33 , 34 ]. OS was induced by exposing experimental rats to the cigarette smoke ((15 cigarettes at once, two times daily) and intermittent hypoxia (with ~99% nitrogen (N 2 ) for 30 s and air (~21% O 2 ) every day for 90 s, 30 times per hour, 8 h per day) for 8 weeks [ 33 , 34 ]. OS rats were, 24 h after cigarette smoke and intermittent hypoxia exposure, randomly divided in experimental groups to intravenously receive either saline or BM-MSCs (2 × 10 6 cells; one time/week, for 4 weeks) [ 33 , 34 ].…”

“…OS was induced by exposing experimental rats to the cigarette smoke ((15 cigarettes at once, two times daily) and intermittent hypoxia (with ~99% nitrogen (N 2 ) for 30 s and air (~21% O 2 ) every day for 90 s, 30 times per hour, 8 h per day) for 8 weeks [ 33 , 34 ]. OS rats were, 24 h after cigarette smoke and intermittent hypoxia exposure, randomly divided in experimental groups to intravenously receive either saline or BM-MSCs (2 × 10 6 cells; one time/week, for 4 weeks) [ 33 , 34 ]. It is well known that injured parenchymal cells release alarmins that attract exogenously administered MSCs to the site of injury [ 21 ].…”

“…It is well known that injured parenchymal cells release alarmins that attract exogenously administered MSCs to the site of injury [ 21 ]. Accordingly, several weeks after their systemic infusion, BM-MSCs were detected in the lungs and aortas which were the most severely injured by cigarette smoke and hypoxia [ 33 , 34 ].…”

BMSC cells alleviate liver injury induced by ulcerative colitis via repairing the intestinal-liver barrier and activating hepatocyte growth factor

“…In the recent years, systemic administration of BMSCs to regulate the immune response and enhance endogenous regeneration is becoming a new treatment strategy in immune hyperactivity and tissue injury diseases [21][22][23]. Intravascular injection of BMSCs has been confirmed to be an effective treatment for autoimmune diseases [24][25], graft vs. host disease (GVHD) [26][27], vascular diseases and diabetes [28][29]. Hundreds of clinical trials of BMSC cell therapy are now being carried out world-wide [30][31][32].…”