Human adipose-derived mesenchymal stem cell spheroids improve recovery in a mouse model of elastase-induced emphysema

Abstract

Emphysema, a pathologic component of the chronic obstructive pulmonary disease, causes irreversible destruction of lung. Many researchers have reported that mesenchymal stem cells can regenerate lung tissue after emphysema. We evaluated if spheroid human adipose-derived mesenchymal stem cells (ASCs) showed greater regenerative effects than dissociated ASCs in mice with elastase-induced emphysema. ASCs were administered via an intrapleural route. Mice injected with spheroid ASCs showed improved regeneration of lung tissues, increased expression of growth factors such as fibroblast growth factor-2 (FGF2) and hepatocyte growth factor (HGF), and a reduction in proteases with an induction of protease inhibitors when compared with mice injected with dissociated ASCs. Our findings indicate that spheroid ASCs show better regeneration of lung tissues than dissociated ACSs in mice with elastase-induced emphysema. [BMB Reports 2017; 50(2): 79-84].

Fig. 1

The expression of apoptotic markers and growth factors. (A) Western blotting images and (B) protein band quantification for BAX and Bcl-2. (C) Western blotting images and (D) protein band quantification for FGF-2 and VEGF. (E) FGF-2 and (F) VEGF production was measured in conditioned media.

Fig. 2

Improved recovery efficacy of ASCs in an elastase-induced mouse model of emphysema. (A) Experimental protocol. (B-E) Lung histology with H and E staining: (B) control (n = 5); (C) elastase only (n = 12); (D) elastase + dissociated ASCs (n = 10); and (E) spheroid ASCs (n = 11) (10×). (F) Mean linear intercept (mean ± SEM). Scale bar = 0.5 mm. ^*P < 0.05 and ^***P < 0.001 for comparisons between 2 groups.

Fig. 3

Growth factor production in lungs with emphysema: (A) FGF-2, (B) HGF, and (C) VEGF. ^*P < 0.05 and ^**P < 0.01 for comparisons between 2 groups.

Fig. 4

Effects of ASCs on MMPs, TIMP-1 and SLPI expression in lungs with emphysema. (A) The mRNA levels of MMP-2, MMP-9, and MMP-12 in the lung. (B) and (C) Representative images for western blotting and gelatin zymography. (D) The mRNA expression of TIMP-1 and SLPI. ^*P < 0.05, ^**P < 0.01, and ^***P < 0.001 for comparisons between 2 groups.