Exosomes from Bone Marrow Mesenchymal Stem Cells Inhibit Neuronal Apoptosis and Promote Motor Function Recovery via the Wnt/β-catenin Signaling Pathway

Abstract

Severe spinal cord injury (SCI) is caused by external mechanical injury, resulting in unrecoverable neurological injury. Recent studies have shown that exosomes derived from bone marrow mesenchymal stem cells (BMSCs-Exos) might be valuable paracrine molecules in the treatment of SCI. In this study, we designed SCI models in vivo and in vitro and then investigated the possible mechanism of successful repair by BMSCs-Exos. In vivo, we established one Sham group and two SCI model groups. The Basso, Beattie, Bresnahan (BBB) scores showed that BMSCs-Exos could effectively promote the recovery of spinal cord function. The results of the Nissl staining, immunohistochemistry, and TUNEL/NeuN/DAPI double staining showed that BMSCs-Exos inhibited neuronal apoptosis. Western blot analysis showed that the protein expression level of Bcl-2 was significantly increased in the BMSCs-Exos group compared with the PBS group, while the protein expression levels of Bax, cleaved caspase-3, and cleaved caspase-9 were significantly decreased. The results of western bolt and qRT-PCR demonstrated that BMSCs-Exos could activate the Wnt/β-catenin signaling pathway effectively. In vitro, we found that inhibition of the Wnt/β-catenin signaling pathway could promote neuronal apoptosis following lipopolysaccharide (LPS) induction. These results demonstrated that BMSCs-Exos may be a promising therapeutic for SCI by activating the Wnt/β-catenin signaling pathway.

<p>Exosomes Derived from MicroRNA-146a-5p-Enriched Bone Marrow Mesenchymal Stem Cells Alleviate Intracerebral Hemorrhage by Inhibiting Neuronal Apoptosis and Microglial M1 Polarization</p>

“…Exos secreted by BMSCs were reported to mediate cell-to-cell communication, signaling pathway activation and decomposition of harmful substances, which may be involved in neuroprotective function. 29,30 MiR-enriched exosomes which are subsequently taken up by target cells could alter gene expression to exert biological functions. 31 The present study demonstrated that Exos derived from BMSCs loaded with miR-146a-5p could effectively alleviate brain injuries post ICH by reducing neuronal apoptosis, and inflammation associated with the suppression of microglial M1 polarization.…”

<p>Bone Marrow Mesenchymal Stem Cell-Derived Exosomes Improves Spinal Cord Function After Injury in Rats by Activating Autophagy</p>

“…8 BMSC-derived exosomes (BMSC-Exos) have been used in animal models of various diseases including reduction of myocardial ischemia, promotion of skin healing, promotion damaged kidney repair and spinal nerves, and inhibition of liver vitaminization. [9][10][11] Studies have also shown that BMSC-Exos have a repairing effect on SCI, but the specific mechanism is unclear.…”

<p>miR106a Promotes the Growth of Transplanted Breast Cancer and Decreases the Sensitivity of Transplanted Tumors to Cisplatin</p>

“…There are studies that confirm this. 18 When β-catenin accumulates to a certain level, it can enter the cell nucleus directly, join TCF4/LEFS, activate downstream CD44, cMyc and cyclin D1 gene expression and transcription, and lead to abnormal cell proliferation. 19…”