Repair of peripheral nerve defects by nerve grafts incorporated with extracellular vesicles from skin-derived precursor Schwann cells

Yu, Miaomei; Gu, Guohao; Ma, Cong; Du, Mingzhi; Wang, Wei; Shen, Mi; Zhang, Qi; Shi, Haiyan; Gu, Xiaosong; Ding, Fei

doi:10.1016/j.actbio.2021.07.026

Cited by 48 publications

(41 citation statements)

References 57 publications

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“…This further aggravates ischemia and hypoxia and activates inflammation, thereby activating the proteolytic pathway, which causes proteolysis and muscle atrophy [ 4 ]. Our previous study found that nerve grafts constructed from SKP-SC-EVs promote angiogenesis, improve the microenvironment, and promote the expression of angiogenesis-related factors, whilst also promoting nerve regeneration [ 41 ]. Therefore, we further explored the potential effect of SKP-SC-EVs on blood flow reperfusion during denervated skeletal muscle atrophy.…”

Section: Resultsmentioning

confidence: 99%

“…We previously confirmed that SKP-SC-EVs promote the axonal growth of the sciatic nerve [ 40 ]. A nerve graft constructed from SKP-SC-EVs can repair peripheral nerve defects [ 41 ]. In addition, our early RNA sequencing analysis showed that SKP-SC-EVs contain a large number of miRNAs, such as miR-30a-5p, miR-22, miRNA-23a/27a, and miR-27b, which have antioxidant and anti-inflammatory properties [ 42 , 43 , 44 , 45 ].…”

Section: Introductionmentioning

confidence: 99%

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SKP-SC-EVs Mitigate Denervated Muscle Atrophy by Inhibiting Oxidative Stress and Inflammation and Improving Microcirculation

et al. 2021

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Denervated muscle atrophy is a common clinical disease that has no effective treatments. Our previous studies have found that oxidative stress and inflammation play an important role in the process of denervated muscle atrophy. Extracellular vesicles derived from skin precursor-derived Schwann cells (SKP-SC-EVs) contain a large amount of antioxidants and anti-inflammatory factors. This study explored whether SKP-SC-EVs alleviate denervated muscle atrophy by inhibiting oxidative stress and inflammation. In vitro studies have found that SKP-SC-EVs can be internalized and caught by myoblasts to promote the proliferation and differentiation of myoblasts. Nutrient deprivation can cause myotube atrophy, accompanied by oxidative stress and inflammation. However, SKP-SC-EVs can inhibit oxidative stress and inflammation caused by nutritional deprivation and subsequently relieve myotube atrophy. Moreover, there is a remarkable dose-effect relationship. In vivo studies have found that SKP-SC-EVs can significantly inhibit a denervation-induced decrease in the wet weight ratio and myofiber cross-sectional area of target muscles. Furthermore, SKP-SC-EVs can dramatically inhibit highly expressed Muscle RING Finger 1 and Muscle Atrophy F-box in target muscles under denervation and reduce the degradation of the myotube heavy chain. SKP-SC-EVs may reduce mitochondrial vacuolar degeneration and autophagy in denervated muscles by inhibiting autophagy-related proteins (i.e., PINK1, BNIP3, LC3B, and ATG7). Moreover, SKP-SC-EVs may improve microvessels and blood perfusion in denervated skeletal muscles by enhancing the proliferation of vascular endothelial cells. SKP-SC-EVs can also significantly inhibit the production of reactive oxygen species (ROS) in target muscles after denervation, which indicates that SKP-SC-EVs elicit their role by upregulating Nrf2 and downregulating ROS production-related factors (Nox2 and Nox4). In addition, SKP-SC-EVs can significantly reduce the levels of interleukin 1β, interleukin-6, and tumor necrosis factor α in target muscles. To conclude, SKP-SC-EVs may alleviate the decrease of target muscle blood perfusion and passivate the activities of ubiquitin-proteasome and autophagy-lysosome systems by inhibiting oxidative stress and inflammatory response, then reduce skeletal muscle atrophy caused by denervation. This study not only enriches the molecular regulation mechanism of denervated muscle atrophy, but also provides a scientific basis for SKP-SC-EVs as a protective drug to prevent and treat muscle atrophy.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

SKP-SC-EVs Mitigate Denervated Muscle Atrophy by Inhibiting Oxidative Stress and Inflammation and Improving Microcirculation

et al. 2021

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“…Moreover, Yu et al generated an artificial nerve graft incorporated with extracellular vesicles derived from skin-derived precursor Schwann cells (SKP-SC-EVs), and bridged a 10-mm long sciatic nerve defect in rats. Compared with silicone conduits and autografts, the newly developed nerve grafts significantly accelerated the recovery of motor, sensory, and electrophysiological functions by facilitating outgrowth and myelination of regenerated axons, as well as alleviating denervation-induced atrophy of target muscles [ 210 ].…”

Section: Exosomes In Peripheral Nerve Repair and Regenerationmentioning

confidence: 99%

The Therapeutic Potential of Exosomes in Soft Tissue Repair and Regeneration

Wan

Hussain

Behfar

et al. 2022

IJMS

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Soft tissue defects are common following trauma and tumor extirpation. These injuries can result in poor functional recovery and lead to a diminished quality of life. The healing of skin and muscle is a complex process that, at present, leads to incomplete recovery and scarring. Regenerative medicine may offer the opportunity to improve the healing process and functional outcomes. Barriers to regenerative strategies have included cost, regulatory hurdles, and the need for cell-based therapies. In recent years, exosomes, or extracellular vesicles, have gained tremendous attention in the field of soft tissue repair and regeneration. These nanosized extracellular particles (30–140 nm) can break the cellular boundaries, as well as facilitate intracellular signal delivery in various regenerative physiologic and pathologic processes. Existing studies have established the potential of exosomes in regenerating tendons, skeletal muscles, and peripheral nerves through different mechanisms, including promoting myogenesis, increasing tenocyte differentiation and enhancing neurite outgrowth, and the proliferation of Schwann cells. These exosomes can be stored for immediate use in the operating room, and can be produced cost efficiently. In this article, we critically review the current advances of exosomes in soft tissue (tendons, skeletal muscles, and peripheral nerves) healing. Additionally, new directions for clinical applications in the future will be discussed.

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“…SDEVs play a regulatory role in the homeostasis of different cell types of the PNS through p75 NTR and sortilin is identified by a small RNA profile ( Gonçalves et al, 2020 ). EVs from skin precursor-derived SCs have been demonstrated to play a crucial role in axonal regrowth and regeneration of neurons ( Wu et al, 2020 ) and repair of peripheral nerve defects by nerve grafts ( Yu et al, 2021 ). Similarly, the transfer of RNA through EVs secreted by SC-like differentiated adipose stem cells has been shown to promote neurite outgrowth ( Ching et al, 2018 ).…”

Section: Various Kinds Of Extracellular Vesicles In Glia-neuron Intra...mentioning

confidence: 99%

Role of Extracellular Vesicles in Glia-Neuron Intercellular Communication

Ahmad

Srivastava

Singh

et al. 2022

Front. Mol. Neurosci.

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Cross talk between glia and neurons is crucial for a variety of biological functions, ranging from nervous system development, axonal conduction, synaptic transmission, neural circuit maturation, to homeostasis maintenance. Extracellular vesicles (EVs), which were initially described as cellular debris and were devoid of biological function, are now recognized as key components in cell-cell communication and play a critical role in glia-neuron communication. EVs transport the proteins, lipids, and nucleic acid cargo in intercellular communication, which alters target cells structurally and functionally. A better understanding of the roles of EVs in glia-neuron communication, both in physiological and pathological conditions, can aid in the discovery of novel therapeutic targets and the development of new biomarkers. This review aims to demonstrate that different types of glia and neuronal cells secrete various types of EVs, resulting in specific functions in intercellular communications.

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Repair of peripheral nerve defects by nerve grafts incorporated with extracellular vesicles from skin-derived precursor Schwann cells

Cited by 48 publications

References 57 publications

SKP-SC-EVs Mitigate Denervated Muscle Atrophy by Inhibiting Oxidative Stress and Inflammation and Improving Microcirculation

SKP-SC-EVs Mitigate Denervated Muscle Atrophy by Inhibiting Oxidative Stress and Inflammation and Improving Microcirculation

The Therapeutic Potential of Exosomes in Soft Tissue Repair and Regeneration

Role of Extracellular Vesicles in Glia-Neuron Intercellular Communication

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