Mesenchymal Stem Cells and Idiopathic Pulmonary Fibrosis Potential for Clinical Testing
Mesenchymal Stem Cells and Idiopathic Pulmonary Fibrosis Potential for Clinical Testing
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DOI：
10.1164/rccm.201207-1204pp
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发表时间：
2013-07-15
影响因子：
24.7
通讯作者：
Glassberg, Marilyn K.
中科院分区：
文献类型：
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作者：
Toonkel, Rebecca L.;Hare, Joshua M.;Glassberg, Marilyn K.
特发性肺纤维化（IPF）是一种进行性、衰弱性和致死性肺部疾病，其特征为间质性纤维化伴肺容量减少和低氧性呼吸衰竭。IPF患者的预后较差，寻求有效治疗一直不成功。尽管在过去的十年里进行了几次临床试验，但美国还没有发现这种药物。S.美国食品药品监督管理局批准的IPF患者治疗，因此无标准治疗。在发病机制方面，IPF的特征是肺泡上皮细胞损伤和活化伴间质性炎症、成纤维细胞增殖伴细胞外基质胶原沉积和肺功能丧失。由于间充质干细胞（MSC）归巢于损伤部位，抑制炎症，并有助于上皮组织修复，因此已建议将其用作治疗IPF的疗法。MSC具有作为多种疾病的新型治疗剂的潜力，并且它们已经在许多临床试验中安全地施用。在肺纤维化动物模型中进行的一些（但不是全部）临床前研究表明，MSC可能有效治疗IPF。鉴于MSC给药在其他患者人群中的安全性和简便性，IPF临床前动物模型的结果，以及这种毁灭性疾病对新型治疗选择的主要需求，我们建议精心设计的MSC治疗IPF患者的临床试验是合适的。确立IPF背景下的安全性是早期临床试验的首要任务，其次是临床和生物学疗效指标。
Idiopathic pulmonary fibrosis (IPF) is a progressive, debilitating, and fatal lung disease characterized by interstitial fibrosis with decreasing lung volumes and hypoxemic respiratory failure. The prognosis for patients with IPF is poor and the quest to find effective therapies has been unsuccessful. Despite several clinical trials over the past decade, there are no U. S. Food and Drug Administration-approved treatments for patients with IPF and thus no standard of care. In terms of pathogenesis, IPF is characterized by alveolar epithelial cell injury and activation with interstitial inflammation, fibroblast proliferation with extracellular matrix collagen deposition, and loss of lung function. Because mesenchymal stem cells (MSCs) home to sites of injury, inhibit inflammation, and contribute to epithelial tissue repair, their use has been suggested as a therapy for the treatment of IPF. MSCs have potential as a novel therapeutic agent in multiple diseases and they have been safely administered in a number of clinical trials. Some, but not all, preclinical studies in animal models of lung fibrosis suggest that MSCs might be effective in the treatment of IPF. Given the safety and ease of MSC administration in other patient populations, the results in preclinical animal models of IPF, and the major need for novel therapeutic options in this devastating disease, we propose that carefully designed clinical trials of MSCs for the treatment of patients with IPF are appropriate. Establishing safety in the setting of IPF is the first priority in early clinical trials followed by clinical and biological measures of efficacy.