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Exosome-shuttled MYCBPAP from bone marrow mesenchymal stem cells regulates synaptic remodeling and ameliorates
Qiuyue Yan1, Yong Yin1, Xuechun Li1
1Department of Neurology, Cangzhou Central Hospital, Cangzhou 061001 Hebei, PR China.
Background And Purpose:
Mesenchymal stem cells (MSC) have been demonstrated to improve cardiac function via the secretion of paracrine factors rather than direct differentiation. We, therefore, investigated whether bone marrow-derived MSC (BMSC)-released exosomes (BMSC-exo) enhance neurological recovery in spontaneously hypertensive rats (SHR) with ischemic stroke.
Methods:
Markers of BMSC and BMSC-exo were detected to characterize BMSC and BMSC-exo. A green fluorescent PKH-67-labeled assay was conducted to ensure BMSC-exo internalization. Rat neuronal cells (RNC) were induced with Ang II and oxygen-glucose deprivation. The protective effects of BMSC-exo on RNC were studied by CCK-8, LDH, and immunofluorescence assays. SHR were subjected to middle cerebral artery occlusion, and the systolic and diastolic blood pressure changes in the modeled rats were measured. The effects of BMSC-exo on SHR were investigated by mNSS scoring, foot-fault tests, immunohistochemistry, Western blot, TTC staining, TUNEL, and HE staining. The hub genes related to SHR and proteins shuttled by BMSC-exo were intersected to obtain a possible candidate, followed by rescue experiments.
Results:
BMSC-exo significantly promoted RNC viability and repressed cell apoptosis and cytotoxicity. Moreover, SHR administrated with BMSC-exo exhibited significant improvement in functional recovery and narrowed infarct size. BMSC-exo shuttled the MYCBPAP protein. Knockdown of MYCBPAP inhibited the protective effects of BMSC-exo on RNC and exacerbated synaptic damage in SHR.
Conclusions:
MYCBPAP shuttled by BMSC-exo facilitates synaptic remodeling in SHR, which may contribute to a therapeutic strategy for ischemic stroke treatment.
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