The effect of adipose stem cell therapy on pulmonary fibrosis induced by repetitive intratracheal bleomycin in mice.

Lee, Sang Hoon; Lee, Eun Joo; Lee, Sang Yeub; Kim, Je Hyeong; Shim, Jae Jeong; Shin, Chol; In, Kwang Ho; Kang, Kyung Ho; Uhm, Chang Sub; Kim, Han-Kyeom; Yang, Kyung-Sook; Park, Sanghoon; Kim, Hyun Soo; Kim, Yong Man; Yoo, Tai June

Adipose stem cells (ASCs) are detectable in the parenchyma and large airways of lungs after systemic administration, and ameliorate inflammatory infiltration and cell death in animal models of emphysema. We evaluated whether ASC treatment could attenuate lung fibrosis induced by repetitive intratracheal bleomycin administration. Male 8-week-old C57BL/6J mice (control group, bleomycin-only group, and bleomycin-plus-ASC group) were used. Eight biweekly doses of bleomycin were injected intratracheally via an intubation procedure at a dose of 0.04 units in a total volume of 100 μL of sterile saline. During the latter 2 months of the 4-month bleomycin exposure, human ASCs (3 × 105 cells) were administered repeatedly via intraperitoneal injection at the same time as bleomycin. Lung tissues were evaluated for histology, collagen content, TUNEL staining, and TGF-β levels. Bronchoalveolar lavage (BAL) was performed for cell counting. Administrations of ASCs ameliorated the deleterious effects of repetitive intratracheal instillation of bleomycin, namely hyperplasia of Club cells (Clara cells) and cuboidal alveolar epithelial cells, infiltration of the perialveolar ducts by inflammatory cells, septal thickening, enlarged alveoli, and extensive fibrosis. Addition of ASC led to suppression of bleomycin-induced epithelial cell apoptosis and expression of TGF-β. These results suggest a useful therapeutic effect of ASCs on pulmonary fibrosis induced by repetitive bleomycin administration. Further studies will be required to evaluate the efficacy of ASC therapy for the treatment of idiopathic pulmonary fibrosis.

ADIPOSE tissues; CELL death; BRONCHOALVEOLAR lavage; BLEOMYCIN; PULMONARY fibrosis; EPITHELIAL cells

Experimental Lung Research, 2014, Vol 40, Issue 3, p117

0190-2148

Academic Journal

10.3109/01902148.2014.881930