Changes in arterial blood gas and pulmonary pathology of experimental pulmonary emphysema following mesenchymal stem cell transplantation in rats

Baoping LI; Xiaojian ZHAO; Yongming SONG; Lei ZHANG; Pengyan LU

ABSTRACT

BACKGROUND:

Pathological changes of pulmonary emphysema are not reversible according to the existent pathogenesis of pulmonary emphysema. Research over many years report that injury of pulmonary blood capillary may take part in new pathogenesis of pulmonary emphysema based on lung volume reduction operation and bronchial lumen occlusion. Mesenchymal stem cells (MSCs) have multi-directional differentiation potencies, such as the differentiation into vascular endothelial cells. Therefore, MSCs may promote pulmonary vascularization and repair pulmonary tissue.

OBJECTIVE:

To observe the effect of MSCs transplantation on pathological changes of arterial blood gas and pulmonary tissue in model rats with pulmonary emphysema, and investigate the therapeutic effects on MSCs on pulmonary emphysema and the pathogenesis of pulmonary emphysema.

DESIGN:

Randomized controlled animal study.

SETTING:

The Second Hospital of Shanxi Medical University.MATERIALS Thirty healthy Wistar rats, 6 weeks old, of either gender, weighing 180-200 g. They were provided by Physiological Experiment Animal Center, Shanxi Medical University. All rats were randomly divided into MSCs treatment group, model group and control group with 10 rats each.

METHODS:

The experiment was carried out in the Physiological Laboratory of Shanxi Medical University from April 2005 to April 2006. Rats in the MSCs treatment group and in the model group were anesthetized and intratracheally perfused with 250 U/kg Porcine pancreatic elastase (PPE) to establish pulmonary emphysema models; while, rats in the control group were perfused with saline. The models were successfully established 4 weeks later. All rats were anesthetized and then femur and tibia were obtained to separate and culture MSCs in vitro. Immunocytochemistry was used to detect the expression of CD71 in order to evaluate MSCs. Bromium azacytidine-labeled MSCs were inserted along caudal vein into rats in the MSCs treatment group; while, rats in the model group and control group were inserted with the same volume of PBS solution.MAIN OUTCOME

MEASURES:

① Changes of arterial blood gas in the three groups; ② Pulmonary tissue was used for pathological sections in order to calculate mean alveolar number, mean alveolar area and mean linear intercept; ③Immunocytochemical staining was used to measure numbers of CD34+ cells so as to determine proliferation of alveolar blood capillary.

RESULTS:

Three rats in all died during the model establishment, while another 3 rats were supplied. Therefore, an overall number of 30 rats were involved in the final analysis. ① Culture and evaluation of MSCs At 3 days after inoculation, MSCs were generally adherent to walls and fusiformly shaped. In the third generation, the expression of CD71 was observed on the surface of MSCs.② Comparisons of arterial blood gas in the three groups There were no significant differences in pH value, PO2, PCO2 and SaO2 in the three groups (P ＞ 0.05). ③ Pathological changes of pulmonary tissue Pathological changes in the MSCs treatment group were milder than those in the model group;meanwhile, mean alveolar number in the MSCs treatment group was more than that in the model group, and there was significant difference between them (F=80.201, P＜ 0.05). While mean alveolar area and mean linear intercept in the MSCs treatment group were smaller than those in the model group, and there were significant differences (F =26.755,26.875, P ＜ 0.05). ④ Comparisons of CD34+ expression in pulmonary tissue Relative positive area of CD34+ in the MSCs treatment group and model group was smaller than that in the control group (F =20.411, P ＜ 0.05), but that in the MSCs treatment group was larger than that in the model group, and there was significant difference between them (F=20.411, P＜ 0.05).

CONCLUSION:

MSCs can reverse the pathological changes of pulmonary emphysema; on the other hand, the decrease of the number of pulmonary capillary maybe one of the important pathogeneses of pulmonary emphysema.