A pH probe inhibits senescence in mesenchymal stem cells

作者：Lihong Wang, Xianjing Han, Guojing Qu, Le Su, Bao‐Xiang Zhao, Jun‐Ying Miao · 发表于：Stem Cell Research & Therapy · 年份：2018 · DOI：10.1186/s13287-018-1081-0 · 被引用次数：40 · 研究领域：ATP Synthase and ATPases Research、Autophagy in Disease and Therapy、Adenosine and Purinergic Signaling

Bone marrow-derived mesenchymal stem cells (BMSCs) are gradually getting attention because of its multi-directional differentiation potential, hematopoietic support, and promotion of stem cell implantation. However, cultured BMSCs in vitro possess a very limited proliferation potential, and the presence of stem cell aging has substantially restricted the effect together with the efficiency in clinical treatment. Recently, increasing attention has been paid to the connection between cellular aging and lysosomal acidification as new reports indicated that vacuolar H + -ATPase (v-ATPase) activity was altered and lysosomal pH was dysregulated in the process of cellular aging. Therefore, promoting lysosomal acidification might contribute to inhibition of cell senescence. Our previous studies showed that a novel small molecule, 3-butyl-1-chloro imidazo [1, 5-a] pyridine-7-carboxylic acid (SGJ), could selectively and sensitively respond to acidic pH with fast response (within 3 min), but whether SGJ can promote lysosomal acidification and inhibit senescence in BMSCs is unknown. Rat BMSCs were cultured based on our system that had been already documented. BMSCs were treated with SGJ and/or Bafilomycin-A1 (Baf-A1). The co-localization between SGJ and lysosomes was assessed by a confocal microscope. Acridine orange (AO) staining and the Lysosensor™ Green DND-189 reagents were used for indicating changes in lysosomal concentration of H + . Changes of senescence were detected by immunobl...