The CCL2/CCR2 axis is critical to recruiting macrophages into acellular nerve allograft bridging a nerve gap to promote angiogenesis and regeneration

Pan, Deng; Acevedo-Cintrón, Jesús A.; Sayanagi, Junichi; Snyder‐Warwick, Alison K.; Mackinnon, Susan E.; Wood, Matthew D.

doi:10.1016/j.expneurol.2020.113363

Cited by 34 publications

(34 citation statements)

References 34 publications

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“…Several experiments have shown that macrophages can induce angiogenesis. Recruitment of macrophages can induce angiogenesis to enhance nerve regeneration [ 133 ]. In addition, reduction or depletion of macrophages suppresses angiogenesis [ 134 ].…”

Section: Exosomes and Tumor Angiogenesismentioning

confidence: 99%

Emerging role of exosomes in cancer progression and tumor microenvironment remodeling

et al. 2022

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Cancer is one of the leading causes of death worldwide, and the factors responsible for its progression need to be elucidated. Exosomes are structures with an average size of 100 nm that can transport proteins, lipids, and nucleic acids. This review focuses on the role of exosomes in cancer progression and therapy. We discuss how exosomes are able to modulate components of the tumor microenvironment and influence proliferation and migration rates of cancer cells. We also highlight that, depending on their cargo, exosomes can suppress or promote tumor cell progression and can enhance or reduce cancer cell response to radio- and chemo-therapies. In addition, we describe how exosomes can trigger chronic inflammation and lead to immune evasion and tumor progression by focusing on their ability to transfer non-coding RNAs between cells and modulate other molecular signaling pathways such as PTEN and PI3K/Akt in cancer. Subsequently, we discuss the use of exosomes as carriers of anti-tumor agents and genetic tools to control cancer progression. We then discuss the role of tumor-derived exosomes in carcinogenesis. Finally, we devote a section to the study of exosomes as diagnostic and prognostic tools in clinical courses that is important for the treatment of cancer patients. This review provides a comprehensive understanding of the role of exosomes in cancer therapy, focusing on their therapeutic value in cancer progression and remodeling of the tumor microenvironment. Graphical Abstract

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Section: Exosomes and Tumor Angiogenesismentioning

confidence: 99%

Emerging role of exosomes in cancer progression and tumor microenvironment remodeling

et al. 2022

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“…Both tissue resident and later hematogenous macrophages secrete vascular endothelial growth factor (VEGF), a proangiogenic factor, recruiting endothelial cells to the nerve gap. 20,21 As blood vessels form, fibroblasts and dedifferentiated SCs migrate along the endothelial basal lamina, forming cords similar in structure to the bands of Büngner in the distal stump. Concurrently, there is an influx of other myeloid cells (ie, eosinophils) and T lymphocytes promoting expression of anti-inflammatory cytokines.…”

Section: Overview Of Nerve Injury and Regenerationmentioning

confidence: 99%

“…Concurrently, there is an influx of other myeloid cells (ie, eosinophils) and T lymphocytes promoting expression of anti-inflammatory cytokines. 21-23 With these elements in place, the healing nerve gap is prepared to receive and guide sprouting axons from the proximal stump to the distal stump. The newly formed matrix of SCs, fibroblasts, and blood vessels in the nerve gap conduct the regenerating axons to the distal nerve stump, where processes proceed to facilitate axon growth to their end-organ targets as described previously.…”

Section: Overview Of Nerve Injury and Regenerationmentioning

confidence: 99%

The Role of the IL-4 Signaling Pathway in Traumatic Nerve Injuries

Daines

Schellhardt

Wood

2021

Neurorehabil Neural Repair

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Following traumatic peripheral nerve injury, adequate restoration of function remains an elusive clinical goal. Recent research highlights the complex role that the immune system plays in both nerve injury and regeneration. Pro-regenerative processes in wounded soft tissues appear to be significantly mediated by cytokines of the type 2 immune response, notably interleukin (IL)-4. While IL-4 signaling has been firmly established as a critical element in general tissue regeneration during wound healing, it has also emerged as a critical process in nerve injury and regeneration. In this context of peripheral nerve injury, endogenous IL-4 signaling has recently been confirmed to influence more than leukocytes, but including also neurons, axons, and Schwann cells. Given the role IL-4 plays in nerve injury and regeneration, exogenous IL-4 and/or compounds targeting this signaling pathway have shown encouraging preliminary results to treat nerve injury or other neuropathy in rodent models. In particular, the exogenous stimulation of the IL-4 signaling pathway appears to promote postinjury neuron survival, axonal regeneration, remyelination, and thereby improved functional recovery. These preclinical data strongly suggest that targeting IL-4 signaling pathways is a promising translational therapy to augment treatment approaches of traumatic nerve injury. However, a better understanding of the type 2 immune response and associated signaling networks functioning within the nerve injury microenvironment is still needed to fully develop this promising therapeutic avenue.

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“…In addition to their function as a guiding structure for Schwann cells and an angiocrine source of secreted factors, the new blood vessels in the conduit support axon regeneration by regulating T lymphocytes. Blood vessel endothelial cells in the conduit induce the accumulation of T lymphocytes, which, in turn, recruit eosinophils [ 50 ]. Eosinophils secrete IL-4, which could be essential for neuronal survival, axon regeneration, and the remyelination of regenerated axons [ 50 , 51 ].…”

Section: Angiogenesis In Peripheral Axon Regenerationmentioning

confidence: 99%

“…Blood vessel endothelial cells in the conduit induce the accumulation of T lymphocytes, which, in turn, recruit eosinophils [ 50 ]. Eosinophils secrete IL-4, which could be essential for neuronal survival, axon regeneration, and the remyelination of regenerated axons [ 50 , 51 ]. Little is known about the significance of T lymphocytes and eosinophils in the spontaneous recovery process.…”

Section: Angiogenesis In Peripheral Axon Regenerationmentioning

confidence: 99%

Extracellular Environment-Controlled Angiogenesis, and Potential Application for Peripheral Nerve Regeneration

Saio

Konishi

Hitomi

et al. 2021

IJMS

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Endothelial cells acquire different phenotypes to establish functional vascular networks. Vascular endothelial growth factor (VEGF) signaling induces endothelial proliferation, migration, and survival to regulate vascular development, which leads to the construction of a vascular plexuses with a regular morphology. The spatiotemporal localization of angiogenic factors and the extracellular matrix play fundamental roles in ensuring the proper regulation of angiogenesis. This review article highlights how and what kinds of extracellular environmental molecules regulate angiogenesis. Close interactions between the vascular and neural systems involve shared molecular mechanisms to coordinate developmental and regenerative processes. This review article focuses on current knowledge about the roles of angiogenesis in peripheral nerve regeneration and the latest therapeutic strategies for the treatment of peripheral nerve injury.

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The CCL2/CCR2 axis is critical to recruiting macrophages into acellular nerve allograft bridging a nerve gap to promote angiogenesis and regeneration

Cited by 34 publications

References 34 publications

Emerging role of exosomes in cancer progression and tumor microenvironment remodeling

Emerging role of exosomes in cancer progression and tumor microenvironment remodeling

The Role of the IL-4 Signaling Pathway in Traumatic Nerve Injuries

Extracellular Environment-Controlled Angiogenesis, and Potential Application for Peripheral Nerve Regeneration

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