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
1Department of Anatomy, Korea University College of Medicine , Inchonro, Seoul , Korea.
Exp Lung Res. 2014 Apr;40(3):117-25. doi: 10.3109/01902148.2014.881930.
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 × 10(5) 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.
全身给药后，脂肪干细胞（ASC）可在肺实质和大气道中被检测到，并能改善肺气肿动物模型中的炎症浸润和细胞死亡。我们评估了ASC治疗是否能减轻经气管内重复注射博来霉素诱导的肺纤维化。使用8周龄雄性C57BL/6J小鼠（对照组、仅注射博来霉素组和博来霉素加ASC组）。通过插管程序经气管内注射八次博来霉素，剂量为0.04单位，总体积为100μL无菌生理盐水，每两周注射一次。在博来霉素暴露的4个月中的后2个月，在注射博来霉素的同时，通过腹腔注射重复给予人ASC（3×10⁵个细胞）。对肺组织进行组织学、胶原蛋白含量、TUNEL染色和TGF-β水平评估。进行支气管肺泡灌洗（BAL）以进行细胞计数。ASC给药改善了经气管内重复滴注博来霉素的有害影响，即Clara细胞（克拉拉细胞）和立方肺泡上皮细胞增生、炎症细胞浸润肺泡周围导管、间隔增厚、肺泡扩大和广泛纤维化。添加ASC导致博来霉素诱导的上皮细胞凋亡和TGF-β表达受到抑制。这些结果表明ASC对重复给予博来霉素诱导的肺纤维化具有有益的治疗作用。需要进一步研究来评估ASC疗法治疗特发性肺纤维化的疗效。
