The tissue-engineered human cornea as a model to study expression of matrix metalloproteinases during corneal wound healing

Couture, Camille; Zaniolo, Karine; Carrier, Patrick; Lake, Jennifer; Patenaude, Julien; Germain, Lucie; Guérin, Sylvain L.

doi:10.1016/j.biomaterials.2015.11.006

Cited by 52 publications

(55 citation statements)

References 67 publications

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“…This is in accordance with findings after fetoscopic procedures [8,11], although increased levels of metalloproteinases in the amniotic fluid of sheep after fetoscopies suggested an active fetal membrane remodeling process [16] as it is found in the wound healing process of skin or cornea [17,18]. Interestingly, mesenchymal progenitor cells from the amnion can be mobilized, proliferate, and maintain their native extracellular matrix production by use of engineered matrices containing migration-and proliferation-inducing factors, such as platelet-derived growth factor, basic fibroblast growth factor, or epidermal growth factor [19].…”

Section: Fetal Membrane Healingsupporting

confidence: 77%

Clinical and Histologic Evaluation of the Hysterotomy Site and Fetal Membranes after Open Fetal Surgery for Fetal Spina Bifida Repair

et al. 2018

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Introduction: Among the risks associated with open fetal surgery, myometrium and fetal membrane issues are vexing problems since they may lead to uterine dehiscence or preterm premature rupture of membranes resulting in uterine rupture or preterm birth or both. The aim of this study was to examine whether stapled and sutured hysterotomy scars demonstrate partial or complete healing. Methods: Hysterotomy sites after open fetal surgery were clinically evaluated in 36 women during Caesarean section, classified into the categories intact, thin, and partially or completely dehiscent, then completely excised and histologically analyzed in 25 cases. The histological examination focused on wound healing of myometrium and fetal membranes. Results: The myometrium was intact, thin, and partially or completely dehiscent in 33, 58, and 9%, respectively. The interval between myelomeningocele repair and delivery did not correlate with the healing process. The myometrium showed a reparative zone (scar) with adjacent avital myometrium tissue, fibrosis, and inflammation with foreign body reaction. The intact myometrium was below 1 mm thickness in 56%. All fetal membranes showed complete dehiscence; in 41% they were completely avital. Conclusion: Our study provides evidence that the myometrium shows scarring with substantial thinning or dehiscence. Fetal membranes do not heal spontaneously. In order to prevent uterine rupture in subsequent pregnancies, we recommend the hysterotomy site to be completely excised after birth.

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Section: Fetal Membrane Healingsupporting

confidence: 77%

Clinical and Histologic Evaluation of the Hysterotomy Site and Fetal Membranes after Open Fetal Surgery for Fetal Spina Bifida Repair

et al. 2018

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“…Using ascorbic acid to promote secretion of extracellular matrix (ECM) by fibroblasts in a procedure known as the self‐assembly approach (Auger, Remy‐Zolghadri, Grenier, & Germain, ; Germain, Carrier, Guérin, Salesse, & Auger, ), we succeeded in the reconstruction of a human, three‐dimensional, tissue‐engineered cornea (hTEC; Carrier et al, ; Germain et al, ; Proulx et al, ). When mechanically wounded, the hTEC triggers processes such as cell migration and proliferation, to allow re‐epithelialization of the damaged tissue, which is found to be very similar to wound healing of a native cornea (Carrier et al, ; Couture et al, ; Zaniolo, Carrier, Guerin, Auger, & Germain, ).…”

Section: Introductionmentioning

confidence: 94%

Contribution of the WNK1 kinase to corneal wound healing using the tissue‐engineered human cornea as an in vitro model

Desjardins

Couture

Germain

et al. 2019

J Tissue Eng Regen Med

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Damage to the corneal epithelium triggers important changes in the extracellular matrix (ECM) to which basal human corneal epithelial cells (hCECs) attach. These changes are perceived by integrin receptors that activate different intracellular signalling pathways, ultimately leading to re‐epithelialization of the injured epithelium. In this study, we investigated the impact of pharmacological inhibition of specific signal transduction mediators on corneal wound healing using both monolayers of hCECs and the human tissue‐engineered cornea (hTEC) as an in vitro 3D model. RNA and proteins were isolated from the wounded and unwounded hTECs to conduct gene profiling analyses and protein kinase arrays. The impact of WNK1 inhibition was evaluated on the wounded hTECs as well as on hCECs monolayers using a scratch wound assay. Gene profiling and protein kinase arrays revealed that expression and activity of several mediators from the integrin‐dependent signaling pathways were altered in response to the ECM changes occurring during corneal wound healing. Phosphorylation of the WNK1 kinase turned out to be the most striking activation event going on during this process. The inhibition of WNK1 by WNK463 reduced the rate of corneal wound closure in both the hTEC and hCECs grown in monolayer compared with their respective negative controls. WNK463 also reduced phosphorylation of the WNK1 downstream targets SPAK/OSR1 in wounded hTECs. These in vitro results allowed for a better understanding of the cellular and molecular mechanisms involved in corneal wound healing and identified WNK1 as a kinase important to ensure proper wound healing of the cornea.

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“…A pro-migratory effect of PRP, which could be demonstrated in this study, might be a possible explanation. Epithelial-mesenchymal interactions occurring in vivo, have beneficial effects during wound healing process [23]. Furthermore, adaption time of corneal cells to PRP media might have been prolonged, due to the presence of additional cellular particles in PRP.…”

Section: Discussionmentioning

confidence: 99%

Effects of three blood derived products on equine corneal cells, an in vitro study

Rushton

Kammergruber

Tichy

et al. 2017

Equine Veterinary Journal

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The tissue-engineered human cornea as a model to study expression of matrix metalloproteinases during corneal wound healing

Cited by 52 publications

References 67 publications

Clinical and Histologic Evaluation of the Hysterotomy Site and Fetal Membranes after Open Fetal Surgery for Fetal Spina Bifida Repair

Clinical and Histologic Evaluation of the Hysterotomy Site and Fetal Membranes after Open Fetal Surgery for Fetal Spina Bifida Repair

Contribution of the WNK1 kinase to corneal wound healing using the tissue‐engineered human cornea as an in vitro model

Effects of three blood derived products on equine corneal cells, an in vitro study

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