Adipose-derived stem/stromal cells with heparin-enhanced anti-inflammatory and antifibrotic effects mitigate induced pulmonary fibrosis in mice
Adipose-derived stem/stromal cells with heparin-enhanced anti-inflammatory and antifibrotic effects mitigate induced pulmonary fibrosis in mice
复制标题
具有肝素增强抗炎和抗纤维化作用的脂肪干/基质细胞可减轻小鼠诱导的肺纤维化
DOI：
10.1016/j.bbrc.2022.08.096
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发表时间：
2022
影响因子：
3.1
通讯作者：
Sato Takako
中科院分区：
文献类型：
--
作者：
Saito Takashi;Kotani Takuya;Suzuka Takayasu;Matsuda Shogo;Takeuchi Tohru;Sato Takako
间质性肺病(ILD)是一种危及生命的病理疾病，可导致呼吸衰竭，通常表现为肺纤维化。虽然使用免疫抑制和抗纤维化药物来治疗，但这些药物的有益效果仍然有限。因此，开发新的肺纤维化治疗策略是至关重要的。间充质干细胞具有多向分化潜能；此外，它们还具有抗炎和抗纤维化作用，并具有调节免疫反应和改变植入部位微环境的能力。脂肪组织中存在大量脂肪来源的间充质干细胞(ASCs)。肝素和低分子肝素(LMWH)介导多种细胞因子和生长因子的分泌，具有细胞迁移和抗纤维化作用。本研究旨在证实低分子肝素激活的ASCs对ILD的治疗作用。小鼠骨髓间充质干细胞(MASCs)在低分子肝素(LMWH)培养液中培养。低分子肝素显著增加MASC的数量，增强其迁移、抗炎和抗纤维化作用。此外，博莱霉素诱导的肺纤维化小鼠被静脉注射低分子肝素活化的MASCS。治疗组ILD大鼠肺组织炎症相关基因的相对mRNA表达明显低于病理模型组。我们的研究结果表明，低分子肝素激活的MASC给药可减少肺纤维化。
Interstitial lung disease (ILD) is a life-threatening pathological condition that causes respiratory failure and often presents as pulmonary fibrosis. Although it is treated using immunosuppressive and antifibrotic agents, the beneficial effects of these agents remain limited. Thus, the development of new therapeutic strategies for lung fibrosis is crucial. Mesenchymal stem/stromal cells (MSCs) have multilineage differentiation potential; additionally, they have anti-inflammatory and antifibrotic effects as well as the ability to modulate the immune response and modify the microenvironment at the site of engraftment. Numerous adipose-derived MSCs (ASCs) are present in the adipose tissue. Heparin and low-molecular-weight heparin (LMWH) mediate the secretion of several cytokines and growth factors with cell migratory and antifibrotic effects. This study aimed to confirm the therapeutic effect of LMWH-activated ASCs on ILD. Mouse ASCs (mASCs) were cultured in an LMWH-supplemented medium. LMWH significantly increased the number of mASC and enhanced their migratory, anti-inflammatory, and antifibrotic effects. Furthermore, mice with bleomycin-induced pulmonary fibrosis were intravenously administered LMWH-activated mASCs. The relative mRNA expression of inflammation-related genes in ILD lungs was significantly lower in the treatment group than in the pathological model group. Our findings suggest that LMWH-activated mASC administration reduces lung fibrosis.