Bone marrow stromal cells‑derived exosomes target DAB2IP to induce microglial cell autophagy, a new strategy for neural stem cell transplantation in brain injury

Abstract

Bone marrow stromal cells (MSCs) are a useful source of stem cells for the treatment of various brain injury diseases due to their abundant supply and fewer ethical problems compared with transplant treatment. However, the clinical application of MSCs is limited due to allograft rejection and immunosuppression in the process of MSCs transplantation. According to previous studies, microglial cell autophagy occurs following co-culture with MSCs. In the present study, exosomes were obtained from MSCs and subsequently characterized using transmission electron microscopy, atomic force microscopy and dynamic light scattering particle size analysis. The type of microRNAs (miRs) found in the exosomes was then analyzed via gene chip. The results demonstrated that microglial cell autophagy could be induced by exosomes. This mechanism was therefore investigated further via reverse transcription-quantitative PCR, western blotting and luciferase assays. These results demonstrated that exosomes from MSCs could induce microglial cell autophagy through the miR-32-mediated regulation of disabled homolog 2-interacting protein, thus providing a theoretical basis for the clinical application of miRs in MSCs.

Exosomes as Neurological Nanosized Machines

“…74 Moreover, Zhou et al showed that, in rats that received the 200 μL of exosomes via the tail vein, there was a reduction in neuronal cell death, an improvement in myelin arrangement, and a reduction in myelin loss, as well as an increase in pericyte/endothelial cell coverage of vascular walls. 75 BMSC exosomes also have a role in the anti-inflammatory response, as demonstrated by Yuan et al 76 BMSC exosomes induce autophagy in microglial cells through miR-32 regulation of DAB2IP. 76 Other studies linked BMSC exosomes to M2 polarization of microglia, confirming their immunomodulation effect.…”

“…75 BMSC exosomes also have a role in the anti-inflammatory response, as demonstrated by Yuan et al 76 BMSC exosomes induce autophagy in microglial cells through miR-32 regulation of DAB2IP. 76 Other studies linked BMSC exosomes to M2 polarization of microglia, confirming their immunomodulation effect. 77 Consequently, BMSC exosomes exhibit a neuroprotective effect.…”

The Neuroprotection Effects of Exosome in Central Nervous System Injuries: a New Target for Therapeutic Intervention

“…Li et al have shown that exosomes from neurons inhibited cell apoptosis and death in TBI by suppression of Rab11a-mediated autophagy, suggesting a detrimental role of autophagy in TBI [93]. Interestingly, in another study conducted by Yuan et al, they found that bone marrow MSCs-derived exosomes decreased ER stress in BV2 cells by induction of disabled homolog 2-interacting protein (DAB2IP)-mediated microglial cell autophagy, suggesting a protective role of exosomes and autophagy in brain injury [94]. The discrepancies may be due to the different source of exosomes and cell types used in these two studies.…”

Cell-Derived Exosomes as Therapeutic Strategies and Exosome-Derived microRNAs as Biomarkers for Traumatic Brain Injury

“…Investigators identified that BM-MSCs-Exos secreted miR-32-3p, which targeted DAB2IP, inducing microglia autophagy without affecting the proliferation and growth of microglia in TBI. In this study, miR-211-3p, miR-188-5p, and miR-465-5p may also have been involved in microglial autophagy; however, the researchers did not study them in depth [ 79 ]. A recent study demonstrated that BM-MSCs-Exos reduced the lesion size, inhibited the expression of Bax and TNF-α, and enhanced the expression of Bcl-2, thereby serving a neuroprotective function by ameliorating early neuroinflammatory responses in TBI mice via modulating the polarization of microglia/macrophages [ 80 ].…”