期刊
STEM CELL RESEARCH & THERAPY
卷 10, 期 -, 页码 -出版社
BMC
DOI: 10.1186/s13287-018-1121-9
关键词
Radiation; Exosomes; Bone marrow mesenchymal stem cell; Differentiation; -Catenin
资金
- Natural Science Foundation of China [81130026, 81672215, 81702182, 81874028]
- National Key Research and Development Program [2016YFC1000805]
- Postgraduate research and innovation project of Chongqing [CYB17143]
- clinical research project of the Second Affiliated Hospital of Army Medical University [2015YLC22]
BackgroundRadiotherapy to cancer patients is inevitably accompanied by normal tissue injury, and the bone is one of the most commonly damaged tissues. Damage to bone marrow mesenchymal stem cells (BM-MSCs) induced by radiation is thought to be a major cause of radiation-induced bone loss. Exosomes exhibit great therapeutic potential in the treatment of osteoporosis, but whether exosomes are involved in radiation-induced bone loss has not been thoroughly elucidated to date. The main purpose of this study is to investigate the role of exosomes derived from BM-MSCs in restoring recipient BM-MSC function and alleviating radiation-induced bone loss.MethodsBM-MSC-derived exosomes were intravenously injected to rats immediately after irradiation. After 28days, the left tibiae were harvested for micro-CT and histomorphometric analysis. The effects of exosomes on antioxidant capacity, DNA damage repair, proliferation, and cell senescence of recipient BM-MSCs were determined. Osteogenic and adipogenic differentiation assays were used to detect the effects of exosomes on the differentiation potential of recipient BM-MSCs, and related genes were measured by qRT-PCR and Western blot analysis. -Catenin expression was detected at histological and cytological levels.ResultsBM-MSC-derived exosomes can attenuate radiation-induced bone loss in a rat model that is similar to mesenchymal stem cell transplantation. Exosome-treated BM-MSCs exhibit reduced oxidative stress, accelerated DNA damage repair, and reduced proliferation inhibition and cell senescence-associate protein expression compared with BM-MSCs that exclusively received irradiation. Following irradiation, exosomes promote -catenin expression in BM-MSCs and restore the balance between adipogenic and osteogenic differentiation.ConclusionsOur findings indicate that BM-MSC-derived exosomes take effects by restoring the function of recipient BM-MSCs. Therefore, exosomes may represent a promising cell-free therapeutic approach for the treatment of radiation-induced bone loss.
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