Exosomes derived from M2 Macrophages Improve Angiogenesis and Functional Recovery after Spinal Cord Injury through HIF-1α/VEGF Axis

Abstract

Exosomes are nano-sized vesicles that contain a variety of mRNAs, miRNAs, and proteins. They are capable of being released by a variety of cells and are essential for cell–cell communication. The exosomes produced by cells have shown protective benefits against spinal cord damage (SCI). Recently, it was discovered that M2 macrophages aid in the angiogenesis of numerous illnesses. However, the functional role of M2 macrophage-derived exosomes on SCI is unclear. Here, we investigate the pro-angiogenesis of M2 macrophage-derived exosomes on SCI. We founded that M2 macrophage exosomes alleviated tissue damage and enhanced functional recovery post-SCI. We discovered that M2 macrophage exosome administration increased angiogenesis after SCI in vivo using immunohistochemistry, immunofluorescence labeling, and Western blot analysis. Additionally, the expression of the pro-angiogenesis factors, HIF-1α and VEGF, were enhanced with the treatment of the M2 macrophage exosomes. Furthermore, we found that M2 macrophage exosomes enhanced neurogenesis after SCI in vivo. In vitro, we found that M2 macrophage exosomes can be taken up by the brain endothelial cell line (bEnd.3) and that they enhanced the tube formation, migration, and proliferation of bEnd.3 cells. Furthermore, by using special siRNA to inhibit HIF-1α expression, we observed that the expression of VEGF decreased, and the tube formation, migration, and proliferation of bEnd.3 cells were attenuated with the treatment of HIF-1α-siRNA. In conclusion, our findings reveal that M2 macrophage exosomes improve neurological functional recovery and angiogenesis post-SCI, and this process is partially associated with the activation of the HIF-1/VEGF signaling pathway.

Osteopontin Promotes Angiogenesis in the Spinal Cord and Exerts a Protective Role Against Motor Function Impairment and Neuropathic Pain after Spinal Cord Injury

“…For the first time, our study confirms OPN’s proangiogenic role after SCI in animal models, as evidenced by the revocation of CD31 immunofluorescent signal enhancement after SCI in OPN knockdown mice. OPN could promote angiogenesis through VEGF and/or AKT pathways, 40,41 as we detected potential modulation of VEGF and AKT phosphorylation mediated by OPN post-SCI in this study. Other underlying mechanisms for OPN’s neuroprotective role may include suppressing inflammation and apoptosis through AKT activation 42 .…”

M2 macrophage-derived exosome-encapsulated microneedles with mild photothermal therapy for accelerated diabetic wound healing

“…For example, Huang et al. revealed that MEs improved angiogenesis after spinal cord injury (SCI) by enhancing the expression of pro-angiogenesis factors (HIF-1α and VEGF) [ 41 ]. Similarly, another study showed that MEs stimulated the angiogenic activities of microvascular endothelial cells in vitro , thereby promoting revascularization after SCI [ 31 ].…”

Highly Bioactive MXene-M2-Exosome Nanocomposites Promote Angiogenic Diabetic Wound Repair through Reconstructing High Glucose-Derived Immune Inhibition

“…Moreover, in a high-glucose microenvironment, FM hydrogel and the released M2-Exo exhibited a synergistic effect in inducing M2 macrophages, which resulted in a significant enhancement of angiogenic behaviors in HUVECs, including proliferation, migration, angiogenesis, and scratch healing ability, through a paracrine mechanism. M2 macrophages are known to constitutively express VEGF, which allowed them to interfere with various stages of the angiogenesis cascade, including promoting endothelial cells proliferation, sprouting, and the formation of neovascular networks. − The in vitro findings supported the role of M2 macrophages in enhancing angiogenesis. In vivo, the M2 macrophages induced by FM-Exo hydrogel secreted abundant VEGF in the wound site, facilitating the sprouting and elongating of blood vessels from existing vessels toward the wound.…”