Pretreatment with G-CSF Could Enhance the Antifibrotic Effect of BM-MSCs on Pulmonary Fibrosis

• Main Authors: Feiyan Zhao, Wei Liu, Shaojie Yue, Lei Yang, Qingzhong Hua, Yan Zhou, Haipeng Cheng, Ziqiang Luo, Siyuan Tang
• Format: Article
• Language: English
• Published: Hindawi Limited 2019-01-01
• Series: Stem Cells International
• Online Access: http://dx.doi.org/10.1155/2019/1726743
• ISSN: 1687-966X; 1687-9678

Granulocyte colony-stimulating factor (G-CSF) can promote the repair of a variety of damaged tissues, but the underlying mechanisms have not yet been fully elucidated. Bone marrow mesenchymal stem cells (BM-MSCs) play an important role in the repair of damaged tissue. The aim of this study was to explore whether pretreating BM-MSCs with G-CSF can promote their ability of homing to the lung after in vitro transplantation via upregulating the CXCR4 expression, potentially markedly increasing the antifibrotic effect of BM-MSCs. The BM-MSCs pretreated with G-CSF were transplanted into a mouse on day 14 after bleomycin injection. The antifibrotic effects of BM-MSCs in mice were tested on day 21 by using pathological examination and collagen content assay. Pretreatment of BM-MSCs with G-CSF significantly promoted their ability of homing to the lung and enhanced their antifibrotic effects. However, knocking down the CXCR4 expression in BM-MSCs significantly inhibited the ability of G-CSF to promote the migration and homing of BM-MSCs to the lung and the resulting antifibrotic effects. We also found that G-CSF significantly increased the CXCR4 expression and AKT phosphorylation in BM-MSCs, and the AKT pathway inhibitor LY294002 significantly diminished the ability of G-CSF to upregulate the CXCR4 expression in BM-MSCs. Pretreatment of BM-MSCs with G-CSF promotes the homing of BM-MSCs to the lung via upregulating the CXCR4 expression, leading to a marked increase in the antifibrotic effects of BM-MSCs. This study provides new avenues for the application of BM-MSCs in the repair of different tissues.