Effects and possible mechanisms of mesenchymal stem cell transplantation on emphysema in rats

Abstract

To explore the effects of transplanting bone marrow mesenehymal stem cells (MSCs) on emphysema in rats and elucidate the possible mechanisms. A total of 24 female Sprague-Dawley rats were randomly divided randomly into 3 groups of control, emphysema and MSCs transplantation (n=8 each). The rat model of emphysema was established by 14-week exposure to cigarette smoking and then MSCs labeled with 4, 6-diamidino-2-phenylindole (DAPI) were injected into recipient rats of MSCs transplantation group via tail veins. At 2 and 4 weeks post-transplantation, engraftment and differentiation of MSCs was determined. At 8 weeks post-transplantation, lung fissure sections were prepared for examining the morphological alterations. The apoptosis of alveolar septal cells was assessed. And the levels of oxidative stress in sera and lung were detected. At 2 and 4 weeks post-transplantation, MSCs labeled with DAPI could be found in recipient lungs, some of which differentiated into type II alveolar epithelial cells. Mean linear intercept was higher in emphysema and MSCs transplantation groups than control group [(111 ± 23) and (90 ± 15) vs (74 ± 10) µm], mean alveolar numbers were lower than control group [(94 ± 22) and (125 ± 15) vs (159 ± 22)/mm²] (all P<0.05); mean linear intercept was higher and mean alveolar numbers were lower in emphysema group than MSCs transplantation group (both P<0.05). The apoptotic index of alveolar wall cells in emphysema group was higher than MSCs transplantation group [(13.5 ± 2.5)% vs (4.8 ± 0.7)%, P<0.05]. Malondialdehyde of sera and lung in emphysema and MSCs transplantation groups was higher than control group [(4.3 ± 0.8), (3.7 ± 0.4) vs (3.0 ± 0.4) nmol/ml, (5.4 ± 0.5), (4.8 ± 0.4) vs (4.2 ± 0.6) nmol/mg, all P<0.05]; malondialdehyde of sera and lung in emphysema group was higher than MSCs transplantation group (both P<0.05). Superoxide dismutase (SOD) of sera and lung in emphysema and MSCs transplantation groups was lower than control group [(8.7 ± 0.8), (9.6 ± 0.7) vs (10.5 ± 0.9) U/ml and (56.3 ± 13.4), (70.2 ± 11.0) vs (84.9 ± 13.0) U/mg, all P<0.05]; SOD of sera and lung in emphysema group was lower than MSCs transplantation group (both P<0.05). MSCs transplantation via tail vein may arrest the progression of emphysema in a cigarette-smoke-induced rat model of emphysema through a differentiation of injected MSCs into type II alveolar epithelial cells and down-regulations of apoptosis and oxidative stress.