Microvesicles: Intercellular messengers in cutaneous wound healing

Laberge, Alexandra; Arif, Syrine; Moulin, Véronique J.

doi:10.1002/jcp.26426

Cited by 33 publications

(37 citation statements)

References 99 publications

(115 reference statements)

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“…However, a great interest has recently arisen for a novel class of cell‐to‐cell messengers known as microvesicles (MVs). It is now accepted that MVs serve as vectors for the intercellular transfer of bioactive molecules during wound healing (Laberge, Arif, & Moulin, ). These small cell‐derived structures (100–1,000 nm in diameter) are released into the extracellular environment by budding of the plasma membrane (Jimenez et al, ).…”

Section: Introductionmentioning

confidence: 99%

α‐2‐Macroglobulin induces the shedding of microvesicles from cutaneous wound myofibroblasts

Laberge

Ayoub

Arif

et al. 2018

Journal Cellular Physiology

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Microvesicles (MVs) are recognized as an important class of cell‐to‐cell messengers. Although the properties of MVs are increasingly documented, the mechanisms regulating MV biogenesis remain debated. Myofibroblasts are a key cellular component of wound healing and have been shown to produce MVs upon stimulation with serum. However, the mediator(s) responsible for the observed effect of serum on MV release have yet to be identified. To isolate the molecule(s) of interest, serum proteins were sequentially separated using chromatography, selective precipitation, and electrophoresis. MV production was assessed throughout the purification and after stimulation of myofibroblasts with two potent purified molecules. α‐2‐Macroglobulin (A2M) was thereby found to dose‐dependently stimulate MV release. We confirmed the presence of the A2M receptor, low‐density lipoprotein receptor‐related protein‐1 (LRP1), on myofibroblasts. Inhibition of LRP1 resulted in a significant decrease in MV production. Together, our results suggest that A2M positively regulates MV shedding through the activation of LRP1 on myofibroblasts.

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Section: Introductionmentioning

confidence: 99%

α‐2‐Macroglobulin induces the shedding of microvesicles from cutaneous wound myofibroblasts

Laberge

Ayoub

Arif

et al. 2018

Journal Cellular Physiology

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“…The membrane proteins could also be components of extracellular vesicles, which are increasingly recognized for their ability to modulate the wound healing process. 16 These potential sources of membrane proteins are not mutually exclusive, as apoptotic cell death triggers the release of apoptotic bodies. 17 This and other responses to local tissue injury (e.g., cell activation in the vicinity of an injury 18 ) are likely to be more prominent in MSTCs or minced tissue, due to the higher total wound edge area compared with larger conventional grafts (since the wound area scales with the circumference of the tissue samples, for this study the total wound area was about 20 • lower in the 10 mm-diameter intact skin, compared with an equivalent volume of 0.5 mm-diameter MSTCs), which is likely to at least partially account for the observed differences in protein release profiles.…”

Section: Discussionmentioning

confidence: 99%

Skin Microcolumns as a Source of Paracrine Signaling Factors

Tam

Purschke

Fuchs

et al. 2020

Advances in Wound Care

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We recently developed the approach of using ''microcolumns'' of autologous full-thickness skin tissue for wound repair. The small size of these micro skin tissue columns (MSTCs, *0.5 mm in diameter) allows donor sites to heal quickly without scarring. Treatment with MSTCs significantly accelerate wound healing, and suppled various skin cell types and skin structures to replenish the wound volume. This technology is now starting clinical use. In this study, we investigate whether MSTCs may also influence wound healing by releasing soluble signaling factors. Approach: Freshly harvested MSTCs were incubated in culture medium for 24 h. The conditioned medium was collected and tested for its effects on migration and proliferation of human dermal fibroblasts, and its ability to induce tube formation by human umbilical vein endothelial cells (HUVECs). Proteins released into the conditioned medium were characterized by multiplex enzymelinked immunosorbent assay (ELISA), and compared with medium conditioned by an equivalent mass of intact full-thickness skin. Results: MSTC-conditioned medium increased fibroblast migration and proliferation, as well as HUVEC tube formation. MSTCs released many soluble factors known to play prominent roles in wound healing. A subset of proteins showed significantly different release profiles compared with intact full-thickness skin. Innovation: The technology for harvesting and using MSTCs to augment wound healing was recently developed as an alternative to conventional autologous skin grafting. This study shows that MSTCs could also function as ''cytokine factories.'' Conclusion: In addition to supplying autologous cells to repopulate the wound volume, MSTCs can also function as a source of growth factors and cytokines to further enhance wound healing.

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“…In normal cellular physiology, EVs are now appreciated as important messengers in orchestrating immune responses during processes, such as wound repair and infection with foreign organism (Laberge et al, 2018;Robbins and Morelli, 2014). Early work in the field revealed that immune cells utilize EVs, particularly exosomes, to mediate antigen presentation with other cells at a systemic level (Raposo et al, 1996;Wolfers et al, 2001;Zitvogel et al, 1998).…”

Section: Extracellular Vesicles As Vehicles Of Immune Evasionmentioning

confidence: 99%

Tumor-derived extracellular vesicles: molecular parcels that enable regulation of the immune response in cancer

Sheehan

D’Souza‐Schorey

2019

Journal of Cell Science

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Extracellular vesicles (EVs) are a heterogeneous collection of membrane-bound vesicles released by cells that contain bioactive cargoes including proteins, lipids and nucleic acids. Multiple subpopulations of EVs have now been recognized and these include exosomes and microvesicles. EVs have been thought to facilitate intercellular and distal communication to bring about various processes that enable tumor progression and metastases. Here, we describe the current knowledge of the functional cargo contained within EVs, with a focus on tumor microvesicles, and review the emerging theory of how EVs support immune suppression in cancer.

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Microvesicles: Intercellular messengers in cutaneous wound healing

Cited by 33 publications

References 99 publications

α‐2‐Macroglobulin induces the shedding of microvesicles from cutaneous wound myofibroblasts

α‐2‐Macroglobulin induces the shedding of microvesicles from cutaneous wound myofibroblasts

Skin Microcolumns as a Source of Paracrine Signaling Factors

Tumor-derived extracellular vesicles: molecular parcels that enable regulation of the immune response in cancer

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