Effects of induced pluripotent stem cell and bone marrow-derived mesenchymal stem cells on cigarette smoke-induced lung damage in rats

Abstract

RATIONALE: Cigarette smoking (CS) is the major cause of chronic obstructive pulmonary disease (COPD) which is the fourth leading cause of death and predicted to be the third by 2030. Administration of bone marrow-derived mesenchymal stem cells (BM-MSC) was reported to attenuate CS-induced emphysema in murine model. This study aimed to investigate the effects of induced pluripotent stem cell derived-MSC (IPSC-MSC) on CS-induced lung damage in comparison to BM-MSC treatment in rats. METHODS: Male Sprague-Dawley rats were randomly divided into four groups. The sham air (SA) group was exposed to fresh air while the other three groups to 4% cigarette smoke (CS) one hour per day for 56 days. During the second half of the smoking period, two doses of 3x106 of IPSC-MSC or BM-MSC cells were injected intravenously via tail vein to the two groups, i.e. IP/CS group or BM/CS group at day 29 and day 43. The SA and CS group were injected with phosphate-buffered saline of the same volume. All rats were sacrificed 24 hours after the last CS exposure. Morphological changes were examined in paraffin-embedded lung sections. Levels of inflammatory markers were measured by ELISA. RESULTS: Both IPSC-MSC and BM-MSC were able to reside in the lung for as long as 14 days with significant higher density of resided IPSC-MSCs. Both treatments shared similar efficacy to attenuate CS-induced lung cell apoptosis, to restore CS-induced reduction of lung IL-10 and to alleviate CS-induced elevation of systemic TGF-β1. CONCLUSION: Our findings suggest that treatment of IPSC-MSC or BM-MSC might be able to slow down CS-induced disease progression, possibly through anti-oxidant, anti-inflammatory and anti-apoptotic properties.