Extracellular Vesicles Secreted by Corneal Myofibroblasts Promote Corneal Epithelial Cell Migration

Yeung, Vincent; Zhang, Tancy C; Yuan, Ling; Parekh, Mohit; Cortinas, John A; Delavogia, Eleni; Hutcheon, Audrey E. K.; Guo, Xiaoqing; Ciolino, Joseph B.

doi:10.3390/ijms23063136

Cited by 18 publications

(13 citation statements)

References 91 publications

(127 reference statements)

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“…CD9 was also detected, although it showed a differential expression, only being identified in exosomes of healthy cells at the level of detection used in this work. On the other hand, CD63 was not detected, which is in line with previous studies of the proteomic profile of the corneal tissues where this protein was also not detected [ 20 ], although in another recent study CD63 was detected in isolated extracellular vesicles of keratocytes, although its levels increased markedly when transformation into fibroblasts occurred [ 52 ], which supports the notion, as shown by our controls, that the cells maintain a stable phenotype.…”

Section: Discussionsupporting

confidence: 93%

Exosomes Released by Corneal Stromal Cells Show Molecular Alterations in Keratoconus Patients and Induce Different Cellular Behavior

et al. 2022

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Exosomes have been related to various disorders, but their study in relation to ocular pathologies has been limited. In this article, we analyze exosomes produced by corneal stromal cells from healthy individuals and from patients with keratoconus. The proteomic study allowed for the identification of 14 new proteins with altered expression, related to molecules previously associated with the pathology. miRNA analysis detected 16 altered species, including miR-184, responsible for familial severe keratoconus. The prediction of its potential biological targets identified 1121 genes, including some related to this pathology. Exosomes produced by keratoconic cells induced a marked increase in the migration of stromal cells and corneal epithelium, while those produced by healthy cells had no effect on stromal cells. Both types of nanovesicles reduced the proliferation of stromal and corneal cells, but those produced by healthy cells had less effect. Exosomes produced by healthy cells had concentration-dependent effects on the transcription of genes encoding proteoglycans by keratoconus cells, with a relative normalization observed at concentrations of 240 µg/mL. These results show the alteration of stromal exosomes in keratoconus and suggest an influence on the development of the pathology, although the use of healthy exosomes could also have therapeutic potential.

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Section: Discussionsupporting

confidence: 93%

Exosomes Released by Corneal Stromal Cells Show Molecular Alterations in Keratoconus Patients and Induce Different Cellular Behavior

et al. 2022

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“…In a similar study, it was shown corneal epithelial-EVs have the capacity to influence the transdifferentiation of human conjunctival and corneal epithelial cells [ 124 ], or EVs pre-treated with thrombospondin-1 promoted tissue remodeling and repair [ 125 ]. More recently, our study examined the paracrine crosstalk from the corneal stromal (keratocytes, fibroblasts, and myofibroblasts) EVs and how they influence corneal epithelial wound healing [ 23 ]. The study provides evidence that corneal myofibroblast EVs compared to keratocyte- or fibroblasts-EVs contain distinct cargo proteins that promote corneal epithelial cell proliferation, migration, and motility.…”

Section: What Roles Do Extracellular Vesicles Play In Corneal Fibrosi...mentioning

confidence: 99%

“…The earliest evidence of EV involvement in corneal wound healing began in 1987 from in vivo rabbit keratectomy research [ 122 ]. The functional role of cell-to-cell communication has shown to be mediated by EVs during corneal wound healing, where the corneal epithelium interacts with stromal keratocytes, fibroblasts, and vascular endothelial cells [ 11 , 12 , 20 , 21 ], while corneal stromal EVs interact with corneal epithelial cells [ 23 ]. In another study, limbal stromal cell derived exosomes have been reported to promote proliferation and regeneration of limbal epithelial cells [ 13 ].…”

Section: Can We Utilize Extracellular Vesicles In Treatments Regiment...mentioning

confidence: 99%

“…In pathological states, aberrant activity of export machinery results in the misexpression of proteins, microRNAs (miRNAs), and other biomolecules [ 13 , 16 , 17 , 18 ]. The relevance of EVs in corneal scarring/fibrosis is gaining considerable traction in relation to physiological and pathological responses to corneal wound healing [ 12 , 19 , 20 , 21 , 22 , 23 ]. Currently, extensive research is being carried out to understand their role and mechanism(s) of action in the occurrence and development of corneal related diseases.…”

Section: Introductionmentioning

confidence: 99%

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Extracellular Vesicles in Corneal Fibrosis/Scarring

Yeung

Boychev

Farhat

et al. 2022

IJMS

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Communication between cells and the microenvironment is a complex, yet crucial, element in the development and progression of varied physiological and pathological processes. Accumulating evidence in different disease models highlights roles of extracellular vesicles (EVs), either in modulating cell signaling paracrine mechanism(s) or harnessing their therapeutic moiety. Of interest, the human cornea functions as a refractive and transparent barrier that protects the intraocular elements from the external environment. Corneal trauma at the ocular surface may lead to diminished corneal clarity and detrimental effects on visual acuity. The aberrant activation of corneal stromal cells, which leads to myofibroblast differentiation and a disorganized extracellular matrix is a central biological process that may result in corneal fibrosis/scarring. In recent years, understanding the pathological and therapeutic EV mechanism(s) of action in the context of corneal biology has been a topic of increasing interest. In this review, we describe the clinical relevance of corneal fibrosis/scarring and how corneal stromal cells contribute to wound repair and their generation of the stromal haze. Furthermore, we will delve into EV characterization, their subtypes, and the pathological and therapeutic roles they play in corneal scarring/fibrosis.

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“…The ECM contributes to cell migration: The ECM regulates cell migration speed and direction, serving as a scaffold for cell migration [ 46 ]. For example, fibronectin promotes fibroblasts and corneal epithelial cell migration, while laminin promotes the migration of many tumor cells [ 47 ]. Moreover, chemotaxis and chemotactic migration rely on the ECM, implying embryonic development and wound healing.…”

Section: Extracellular Matrix (Ecm)mentioning

confidence: 99%

Three-Dimensional Bioprinting of Decellularized Extracellular Matrix-Based Bioinks for Tissue Engineering

Zhang

et al. 2022

Molecules

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Three-dimensional (3D) bioprinting is one of the most promising additive manufacturing technologies for fabricating various biomimetic architectures of tissues and organs. In this context, the bioink, a critical element for biofabrication, is a mixture of biomaterials and living cells used in 3D printing to create cell-laden structures. Recently, decellularized extracellular matrix (dECM)-based bioinks derived from natural tissues have garnered enormous attention from researchers due to their unique and complex biochemical properties. This review initially presents the details of the natural ECM and its role in cell growth and metabolism. Further, we briefly emphasize the commonly used decellularization treatment procedures and subsequent evaluations for the quality control of the dECM. In addition, we summarize some of the common bioink preparation strategies, the 3D bioprinting approaches, and the applicability of 3D-printed dECM bioinks to tissue engineering. Finally, we present some of the challenges in this field and the prospects for future development.

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Extracellular Vesicles Secreted by Corneal Myofibroblasts Promote Corneal Epithelial Cell Migration

Cited by 18 publications

References 91 publications

Exosomes Released by Corneal Stromal Cells Show Molecular Alterations in Keratoconus Patients and Induce Different Cellular Behavior

Exosomes Released by Corneal Stromal Cells Show Molecular Alterations in Keratoconus Patients and Induce Different Cellular Behavior

Extracellular Vesicles in Corneal Fibrosis/Scarring

Three-Dimensional Bioprinting of Decellularized Extracellular Matrix-Based Bioinks for Tissue Engineering

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