Pulmonary fibrosis (PF) is a chronic, progressive, fibrotic interstitial disease of the lung with poor prognosis and without effective treatment currently. Data from previous coronavirus infections, such as the Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome, as well as current clinical evidence from the Coronavirus disease 2019 (COVID-19), support that SARS-CoV-2 infection may lead to PF, seriously impacting patient prognosis and quality of life. Therefore, effective prevention and treatment of PF will improve patient prognosis and reduce the overall social and economic burdens. Stem cells, especially mesenchymal stem cells (MSCs) have many great advantages, including migration to damaged lung tissue and secretion of various paracrine factors, thereby regulating the permeability of endothelial and epithelial cells, reducing inflammatory response, promoting tissue repair and inhibiting bacterial growth. Clinical trials of MSCs for the treatment of acute lung injury, PF and severe and critically ill COVID-19 are ongoing. The purpose of this study is to systematically review preclinical studies, explored the effectiveness of MSCs in the treatment of bleomycin (BLM)-induced pulmonary fibrosis and analyze the potential mechanism, combined with clinical trials of current MSCs for idiopathic pulmonary fibrosis (IPF) and COVID-19, so as to provide support for clinical research and transformation of MSCs. Searching PubMed and Embase (− 2021.4) identified a total of 36 preclinical studies of MSCs as treatment of BLM-induced acute lung injury and PF in rodent models. Most of the studies showed the MSCs treatment to reduce BLM-induced lung tissue inflammatory response, inflammatory cell infiltration, inflammatory cytokine expression, extracellular matrix production and collagen deposition, and to improve Ashcroft score. The results of present studies indicate that MSCs may serve as a potential therapeutic modality for the treatment of PF, including viral-induced PF and IPF.

中文翻译：

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间充质干细胞对博莱霉素诱导的肺纤维化的有效性：系统评价和临床应用意义

肺纤维化（pulmonary fibrosis，PF）是一种慢性、进行性、纤维化的肺间质疾病，预后较差，目前尚无有效治疗方法。来自先前冠状病毒感染的数据，例如严重急性呼吸系统综合症 (SARS) 和中东呼吸系统综合症，以及来自 2019 年冠状病毒病 (COVID-19) 的当前临床证据，支持 SARS-CoV-2 感染可能导致PF，严重影响患者预后和生活质量。因此，有效预防和治疗PF将改善患者预后并减轻整体社会和经济负担。干细胞，特别是间充质干细胞（MSCs）具有许多巨大的优势，包括迁移到受损肺组织和分泌各种旁分泌因子，从而调节内皮细胞和上皮细胞的通透性，减少炎症反应，促进组织修复和抑制细菌生长。MSCs 治疗急性肺损伤、PF 和重症和危重症 COVID-19 的临床试验正在进行中。本研究旨在系统回顾临床前研究，探讨间充质干细胞治疗博莱霉素（BLM）诱导的肺纤维化的有效性并分析其潜在机制，并结合目前间充质干细胞治疗特发性肺纤维化（IPF）的临床试验和COVID-19，从而为 MSCs 的临床研究和转化提供支持。搜索 PubMed 和 Embase (- 2021.4) 确定了总共 36 项 MSCs 的临床前研究，用于治疗啮齿动物模型中 BLM 诱导的急性肺损伤和 PF。大多数研究表明，MSCs 治疗可减少 BLM 诱导的肺组织炎症反应，炎症细胞浸润、炎症细胞因子表达、细胞外基质产生和胶原沉积，并提高 Ashcroft 评分。目前的研究结果表明，间充质干细胞可作为治疗 PF 的潜在治疗方式，包括病毒诱导的 PF 和 IPF。