Zhang Enguo, Yang Ye, Zhang Juan, Ding Guoyong, Chen Shangya, Peng Cheng, Lavin Martin F, Yeo Abrey J, Du Zhongjun, Shao Hua
Department of Toxicology, Shandong Academy of Occupational Health and Occupational Medicine, Shandong Academy of Medical Sciences, Jinan, Shandong 250062, P.R. China.
School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences, Jinan, Shandong 250062, P.R. China.
Exp Ther Med. 2019 Mar;17(3):2247-2255. doi: 10.3892/etm.2019.7205. Epub 2019 Jan 28.
Previous studies have demonstrated that bone marrow mesenchymal stem cell (BMSC) transplantation is a promising treatment strategy for pulmonary fibrosis. Although encouraging results have been obtained using animal models of bleomycin (BLM)-induced pulmonary fibrosis, it is evident that transplantation of BMSCs at various time-points after BLM administration has produced different results in terms of treatment efficacy. To shed light on the potential utility of BMSCs for the treatment of lung disease, the present study performed a meta-analysis to estimate the efficacy of BMSCs in animal models of BLM-induced pulmonary fibrosis, and compare early transplantation (BMSCs injected on the same day after administration of BLM) with late transplantation (BMSCs injected on the 14th day after administration of BLM). Relevant studies were retrieved from the MEDLINE, PubMed, Chinese Knowledge Infrastructure and WanFang databases using a comprehensive search approach. A total of 6 studies involving 228 model rats were included. Meta-analysis indicated that early BMSC transplantation was able to prevent or reduce BLM-induced alveolitis and pulmonary fibrosis, while late BMSC transplantation was able to reduce alveolitis, but there was no significant evidence regarding improvement of pulmonary fibrosis. Although BMSC therapy was identified to be generally beneficial in rodent models of BLM-induced pulmonary fibrosis, the efficacy of early transplantation appears to be more satisfactory; overall, the efficacy of transplantation of BMSCs at the acute inflammatory phase was more effective compared with that at the chronic fibrosis stage. Of note, regarding alveolitis and pulmonary fibrosis scores after late transplantation of BMSCs, the sensitivity analysis revealed that the scores were less stable; thus, this result must be interpreted with caution. Furthermore, the quality and methodology of the included studies was comparatively low. Therefore, higher-quality and more rigorous studies are required to validate the results of the present meta-analysis in the future.
先前的研究表明，骨髓间充质干细胞（BMSC）移植是一种很有前景的肺纤维化治疗策略。尽管使用博来霉素（BLM）诱导的肺纤维化动物模型已取得了令人鼓舞的结果，但显然在BLM给药后的不同时间点移植BMSCs在治疗效果方面产生了不同的结果。为了阐明BMSCs在治疗肺部疾病方面的潜在效用，本研究进行了一项荟萃分析，以评估BMSCs在BLM诱导的肺纤维化动物模型中的疗效，并比较早期移植（在BLM给药当天注射BMSCs）和晚期移植（在BLM给药后第14天注射BMSCs）。使用综合检索方法从MEDLINE、PubMed、中国知网和万方数据库中检索相关研究。共纳入6项研究，涉及228只模型大鼠。荟萃分析表明，早期BMSC移植能够预防或减轻BLM诱导的肺泡炎和肺纤维化，而晚期BMSC移植能够减轻肺泡炎，但没有显著证据表明肺纤维化有所改善。尽管在BLM诱导的肺纤维化啮齿动物模型中确定BMSC治疗总体上是有益的，但早期移植的疗效似乎更令人满意；总体而言，在急性炎症期移植BMSCs的疗效比慢性纤维化阶段更有效。值得注意的是，关于BMSCs晚期移植后的肺泡炎和肺纤维化评分，敏感性分析显示评分不太稳定；因此，对这一结果的解释必须谨慎。此外，纳入研究的质量和方法相对较低。因此，未来需要更高质量、更严谨的研究来验证本荟萃分析的结果。
