Human ESC‐sEVs alleviate age‐related bone loss by rejuvenating senescent bone marrow‐derived mesenchymal stem cells
| العنوان: | Human ESC‐sEVs alleviate age‐related bone loss by rejuvenating senescent bone marrow‐derived mesenchymal stem cells |
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| المؤلفون: | Yang Wang, Zongping Xie, Guowen Hu, Juntao Zhang, Yu Chen, Qing Li, Zhifeng Deng, Xin Niu, Bi Chen, Liangzhi Gong, Ji Yuan, Yongjin Sun |
| المصدر: | Journal of Extracellular Vesicles article-version (VoR) Version of Record Journal of Extracellular Vesicles, Vol 9, Iss 1 (2020) |
| بيانات النشر: | Wiley, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Senescence, Histology, bone marrow MSCs, Biology, Transcriptome, 03 medical and health sciences, 0302 clinical medicine, bone loss, medicine, cellular senescence, lcsh:QH573-671, lcsh:Cytology, Mesenchymal stem cell, Wnt signaling pathway, Cell Biology, Extracellular vesicle, embryonic stem cells, Embryonic stem cell, Cell biology, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Bone marrow, Stem cell, Research Article |
| الوصف: | Tissue-resident stem cell senescence leads to stem cell exhaustion, which is a major cause of physiological and pathological ageing. Stem cell-derived extracellular vesicles (SC-EVs) have been reported in preclinical studies to possess therapeutic potential for diverse diseases. However, whether SC-EVs can rejuvenate senescent tissue stem cells to prevent age-related disorders still remains unknown. Here, we show that chronic application of human embryonic stem cell-derived small extracellular vesicles (hESC-sEVs) rescues the function of senescent bone marrow mesenchymal stem cells (BM-MSCs) and prevents age-related bone loss in ageing mice. Transcriptome analysis revealed that hESC-sEVs treatment upregulated the expression of genes involved in antiaging, stem cell proliferation and osteogenic differentiation in BM-MSCs. Furthermore, liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis identified 4122 proteins encapsulated in hESC-sEVs. Bioinformatics analysis predicted that the protein components in the hESCs-sEVs function in a synergistic way to induce the activation of several canonical signalling pathways, including Wnt, Sirtuin, AMPK, PTEN signalling, which results in the upregulation of antiaging genes in BM-MSCs and then the recovery of senescent BM-MSCs function. Collectively, our findings reveal the effect of hESC-sEVs in reversing BM-MSCs senescence and age-related osteogenic dysfunction, thereby preventing age-related bone loss. Because hESC-sEVs could alleviate senescence of tissue-resident stem cells, they might be promising therapeutic candidates for age-related diseases. |
| تدمد: | 2001-3078 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0208a9e721469ed2ad9fd49373e8f474 https://doi.org/10.1080/20013078.2020.1800971 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....0208a9e721469ed2ad9fd49373e8f474 |
| قاعدة البيانات: | OpenAIRE |
PDF full text from Publisher | تدمد: | 20013078 |
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