Regenerative medicine in the treatment of idiopathic pulmonary fibrosis: current position.
Regenerative medicine in the treatment of idiopathic pulmonary fibrosis: current position.
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DOI：
10.2147/sccaa.s49801
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Rojas M
中科院分区：
文献类型：
--
作者：
Álvarez D;Levine M;Rojas M
特发性肺纤维化（IPF）是一种进行性、不可逆的肺部疾病，除移植外没有其他持久的治疗选择。其特征在于正常肺组织被纤维化瘢痕、蜂窝和肌成纤维细胞水平增加所替代。IPF的根本原因在很大程度上仍然未知。目前综述的重点是干细胞治疗的可能用途，特别是间充质干细胞（MSC），一种多能基质细胞群，已在多种肺纤维化（PF）动物模型中显示出有希望的数据。研究最多的MSC来源是骨髓，尽管它们也可以在脂肪组织和脐带以及胎盘中发现。MSC具有免疫调节和组织保护特性，使它们能够操纵受损组织的局部环境，改善炎症并促进修复。由于IPF主要影响老年患者，因此衰老问题与疾病的许多方面存在内在联系，包括干细胞的年龄。动物模型已经显示MSC治疗在减轻博来霉素诱导的PF的纤维化作用方面的成功。然而，博来霉素是PF最常用的模型，在模拟人类中存在的IPF方面是不完美的，因为疾病的持续时间是不平行或不可逆的，并且不会产生蜂窝。此外，MSC剂量的时间已被证明在确定细胞是否最终对疾病进展具有积极或消极影响方面是至关重要的，因为已经证明MSC的最大有益作用发生在疾病的早期炎症阶段，而在晚期纤维化阶段没有或没有负面影响。因此，目前所有的MSC和IPF的临床试验，虽然有希望，但在我们走向真正的干细胞治疗这种疾病时，应该谨慎进行。
Idiopathic pulmonary fibrosis (IPF) is a progressive, irreversible disease of the lung that has no lasting option for therapy other than transplantation. It is characterized by replacement of the normal lung tissue by fibrotic scarring, honeycombing, and increased levels of myofibroblasts. The underlying causes of IPF are still largely unknown. The focus of the current review is the possible use of stem cell therapy, specifically mesenchymal stem cells (MSCs), a multipotent stromal cell population, which have demonstrated promising data in multiple animal models of pulmonary fibrosis (PF). The most studied source of MSCs is the bone marrow, although they can be found also in the adipose tissue and umbilical cord, as well as in the placenta. MSCs have immunomodulatory and tissue-protective properties that allow them to manipulate the local environment of the injured tissue, ameliorating the inflammation and promoting repair. Because IPF primarily affects older patients, the issue of aging is intrinsically linked to many aspects of the disease, including the age of the stem cells. Animal models have shown the success of MSC therapy in mitigating the fibrotic effects of bleomycin-induced PF. However, bleomycin, the most commonly used model for PF, is imperfect in mimicking IPF as it presents in humans, as the duration of the illness is not parallel or reversible, and honeycombing is not produced. Furthermore, the time of MSC dosage has proven to be critical in determining whether the cells will ultimately have a positive or negative effect on disease progression, since it has been demonstrated that the maximal beneficial effect of MSCs occurs during the early inflammatory phase of the disease and that there is no or negative effect during the late fibrotic phase. Therefore, all the current clinical trials of MSCs and IPF, though promising, should proceed with caution as we move toward true stem cell therapy for this disease.