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Kyung-Sun Na, Gabriella Maria Fernandes Cunha, Hyun Jong Lee, Ali R Djalilian, David Myung; Suppression of alkali burn-induced corneal injury by mesenchymal stem cells encapsulated within crosslinked collagen gels. Invest. Ophthalmol. Vis. Sci. 2018;59(9):4375.
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Corneal inflammation after alkaline burns often results in neovascularization and corneal opacification. Although mesenchymal stem cells (MSCs) and their secreted factors (secretome) have been studied for their anti-inflammatory properties, topical instillation is difficult to achieve a good treatment effect due to rapid washout. We proposed that encapsulating hMSCs onto the ocular surface within collagen gels crosslinked with multifunctional PEG succinimidyl esters may be a useful way to deliver the secretome from immobilized MSCs to effectively suppress alkaline-burn induced corneal injury.
Collagen was neutralized and MSCs were added to the solution. Four-arm PEG-N-hydroxysuccinimide (NHS) was subsequently mixed with the neutralized collagen solution to the desired concentration. Collagen gel rheology as a function of the concentration of 4arm PEG-NHS was analyzed to find the optimal cell density for encapsulation of MSCs. In vitro gel degradation and growth factor releases studies were also carried out. An ex vivo organ culture was conducted using rabbit corneas subsequent to alkali-burn injury, and MSCs encapsulated within crosslinked collagen gelswere added to the wounded cornea. The corneas were photographed and fixed for immunohistochemical evaluation. The controls group were collagen 4 arm PEG gels without cells, injury with no treatment, and no injury.
The degradation and rheological properties of different concentration of gels revealed the optimum concentration of 4-arm PEG NHS, collagen, and MSCs for sustained release of the secretome. All corneas in ex vivo organ culture lost their transparency immediately after alkali burn, and only the group treated with collagen-PEG-encapsulated MSCs recovered transparency after 10 days. Immunohistochemistry and confocal microscopy revealed the presence of α–smooth muscle actin (α-SMA) in the superior corneal stroma and epithelium layer of the no treatment group (indicative of fibrotic healing), while no SMA was detected in the treatment group.
Encapsulating MSCs within collagen-PEG gels may be a promising platform for delivering their therapeutic benefits in cases of ocular inflammatory diseases such as alkali-burn injuries.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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