Engineered extracellular vesicles derived from primary M2 macrophages with anti-inflammatory and neuroprotective properties for the treatment of spinal cord injury

Zhang, Chuanjie; Li, Daoyong; Hu, Hengshuo; Wang, Zhe; An, Jinyu; Gao, Zhanshan; Zhang, Kaihua; Mei, Xifan; Wu, Chao; Tian, He

doi:10.1186/s12951-021-01123-9

Cited by 32 publications

(20 citation statements)

References 46 publications

(48 reference statements)

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“…100 NGF bound to macrophage vesicles via MMP9 and is precisely released at the site of injury. In vitro experiments confirmed that EVs-cl-NGF had no toxic effect on neural cells (Figure 4 55 target the inflammatory site in mice within 2 h, peaking at 12 h. In vitro experiments confirmed that Cur@EVs induced a considerable reduction in the expression of proinflammatory factors-that was, TNF-α, IL-1β, and IL-6and an increase in the expression of anti-inflammatory factors (TGF-β), the proportion of M1 macrophage subsets decreasing to 26.90%, and the proportion of the M2 macrophage subset increasing to 31.77% (Figure 4(d)).…”

Section: Gels/scaffolds That Deliver Signaling Moleculesmentioning

confidence: 74%

Biomaterials delivery strategies to repair spinal cord injury by modulating macrophage phenotypes

et al. 2022

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Spinal cord injury (SCI) causes tremendous harm to a patient’s physical, mental, and financial health. Moreover, recovery of SCI is affected by many factors, inflammation is one of the most important as it engulfs necrotic tissue and cells during the early stages of injury. However, excessive inflammation is not conducive to damage repair. Macrophages are classified into either blood-derived macrophages or resident microglia based on their origin, their effects on SCI being two-sided. Microglia first activate and recruit blood-derived macrophages at the site of injury—blood-borne macrophages being divided into pro-inflammatory M1 phenotypes and anti-inflammatory M2 phenotypes. Among them, M1 macrophages secrete inflammatory factors such as interleukin-β (IL-β), tumor necrosis factor-α (TNF-α), IL-6, and interferon-γ (IFN-γ) at the injury site, which aggravates SCIs. M2 macrophages secrete IL-4, IL-10, IL-13, and neurotrophic factors to inhibit the inflammatory response and inhibit neuronal apoptosis. Consequently, modulating phenotypic differentiation of macrophages appears to be a meaningful therapeutic target for the treatment of SCI. Biomaterials are widely used in regenerative medicine and tissue engineering due to their targeting and bio-histocompatibility. In this review, we describe the effects of biomaterials applied to modulate macrophage phenotypes on SCI recovery and provide an outlook.

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Section: Gels/scaffolds That Deliver Signaling Moleculesmentioning

confidence: 74%

Biomaterials delivery strategies to repair spinal cord injury by modulating macrophage phenotypes

et al. 2022

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“…Recently, a new method that improves bioavailability by combining curcumin with extracellular vesicles was reported. 55 In the study, 120-nm engineered extracellular vesicles derived from primary M2 macrophages were used and nerve growth factors and curcumin were combined. The extracellular vesicles could effectively accumulate curcumin at the site of SCIs and inhibit uncontrollable inflammatory responses induced by secondary injury.…”

Section: Obstacles and Future Directionmentioning

confidence: 99%

“…PA–C also enhanced neuroprotection, axonal development, and functional recovery in acute SCIs. Recently, a new method that improves bioavailability by combining curcumin with extracellular vesicles was reported [ 55 ]. In the study, 120-nm engineered extracellular vesicles derived from primary M2 macrophages were used and nerve growth factors and curcumin were combined.…”

Section: Obstacles and Future Directionmentioning

confidence: 99%

Curcumin as a Promising Neuroprotective Agent for the Treatment of Spinal Cord Injury: A Review of the Literature

et al. 2022

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Curcumin is a polyphenolic chemical derived from the rhizomes of Curcuma longa. It has been used throughout the Indian subcontinent for medicinal purposes, religious events, and regional cuisine. It has various pharmacological benefits owing to its anti-inflammatory and antioxidant properties. Its neuroprotective effects on the brain and peripheral nerves have been demonstrated in several in vivo neuronal tissue studies. Because of these functional properties of curcumin, it is considered to have great potential for use in the treatment of spinal cord injuries (SCIs). Numerous immunopathological and biochemical studies have reported that curcumin can help prevent and alleviate subsequent secondary injuries, such as inflammation, edema, free radical damage, fibrosis, and glial scarring, after a primary SCI. Furthermore, following SCI, curcumin administration resulted in better outcomes of neurological function recovery as per the Basso, Beattie, and Bresnahan locomotor rating scale. However, to date, its utility in treating SCIs has only been reported in laboratories. More studies on its clinical applications are needed in the future for ensuring its bioavailability across the blood-brain barrier and for verifying the safe dose for treating SCIs in humans.

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“…Exosomes with good biocompatibility are likely to play an important role in the clinical application of SCI [ 6 , 7 ]. Exosomes can effectively promote functional recovery after SCI through their immunomodulatory, anti-inflammatory [ 8 , 9 ], and antiapoptotic effects as well as their role in promoting vascular and axon regeneration [ 10 , 11 ]. However, the specific mechanism is not clear and remains to be explored.…”

Section: Introductionmentioning

confidence: 99%

Biocompatible exosome-modified fibrin gel accelerates the recovery of spinal cord injury by VGF-mediated oligodendrogenesis

Yang

Dong

et al. 2022

J Nanobiotechnol

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Exosomes show potential for treating patients with spinal cord injury (SCI) in clinical practice, but the underlying repair mechanisms remain poorly understood, and biological scaffolds available for clinical transplantation of exosomes have yet to be explored. In the present study, we demonstrated the novel function of Gel-Exo (exosomes encapsulated in fibrin gel) in promoting behavioural and electrophysiological performance in mice with SCI, and the upregulated neural marker expression in the lesion site suggested enhanced neurogenesis by Gel-Exo. According to the RNA-seq results, Vgf (nerve growth factor inducible) was the key regulator through which Gel-Exo accelerated recovery from SCI. VGF is related to myelination and oligodendrocyte development according to previous reports. Furthermore, we found that VGF was abundant in exosomes, and Gel-Exo-treated mice with high VGF expression indeed showed increased oligodendrogenesis. VGF was also shown to promote oligodendrogenesis both in vitro and in vivo, and lentivirus-mediated VGF overexpression in the lesion site showed reparative effects equal to those of Gel-Exo treatment in vivo. These results suggest that Gel-Exo can thus be used as a biocompatible material for SCI repair, in which VGF-mediated oligodendrogenesis is the vital mechanism for functional recovery.

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Engineered extracellular vesicles derived from primary M2 macrophages with anti-inflammatory and neuroprotective properties for the treatment of spinal cord injury

Cited by 32 publications

References 46 publications

Biomaterials delivery strategies to repair spinal cord injury by modulating macrophage phenotypes

Biomaterials delivery strategies to repair spinal cord injury by modulating macrophage phenotypes

Curcumin as a Promising Neuroprotective Agent for the Treatment of Spinal Cord Injury: A Review of the Literature

Biocompatible exosome-modified fibrin gel accelerates the recovery of spinal cord injury by VGF-mediated oligodendrogenesis

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