期刊
STEM CELLS TRANSLATIONAL MEDICINE
卷 10, 期 3, 页码 374-384出版社
OXFORD UNIV PRESS
DOI: 10.1002/sctm.20-0301
关键词
brain‐ derived neurotropic factor; extracellular vesicles; intraventricular hemorrhage; mesenchymal stem cells
资金
- SMC-Ottogi Research Fund [SMX1200831]
- ICT & Future Planning/the Ministry of Education, Science and Technology [2020R1A2C2010645, 2017R1A2B2011383]
- National Research Foundation of Korea
- Ministry of Health & Welfare, Republic of Korea [HI14C3484]
- Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI)
This study confirmed the efficacy of MSC-derived EVs in attenuating severe IVH-induced brain injuries, showing that the neuroprotection is primarily achieved through BDNF transfer via EVs, which is as effective as parental MSCs.
Brain-derived neurotropic factor (BDNF), which is secreted by mesenchymal stem cells (MSCs), protects against severe intraventricular hemorrhage (IVH)-induced brain injuries. Although the paracrine protective effects of MSCs are mediated primarily by extracellular vesicles (EVs), the therapeutic efficacy of MSC-derived EVs and the role of the BDNF in the EVs have not been studied. This study aimed to determine whether MSC-derived EVs attenuate severe IVH-induced brain injuries, and if so, whether this protection is mediated by BDNF transfer. We compared the therapeutic efficacy of MSCs, MSC-derived EVs with or without BDNF knockdown, and fibroblast-derived EVs in vitro in rat cortical neuronal cells challenged with thrombin and in vivo in newborn rats by injecting 200 mu L of blood at postnatal day (P) 4 and transplanting 1 x 10(5) MSCs or 20 mu g of EVs at P6. The MSCs and MSC-derived EVs, but not the EVs derived from BDNF-knockdown MSCs or fibroblasts, significantly attenuated in vitro thrombin-induced neuronal cell death and in vivo severe IVH-induced brain injuries such as increased neuronal cell death, astrogliosis, and inflammatory responses; reduced myelin basic protein and neurogenesis; led to progression of posthemorrhagic hydrocephalus; and impaired behavioral test performance. Our data indicate that MSC-derived EVs are as effective as parental MSCs in attenuating severe IVH-induced brain injuries, and this neuroprotection is primarily mediated by BDNF transfer via EVs.
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