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Sunil Chauhan, Yinan Lan; Kinetics and Function of Bone Marrow-Derived Mesenchymal Stem Cells in Corneal Injury. Invest. Ophthalmol. Vis. Sci. 2011;52(14):5122.
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Bone marrow-derived mesenchymal stem cells (MSC) are multipotent stem cells which have enormous therapeutic potential due to their (i) multi-lineage differentiation potential; (ii) trophic and anti-inflammatory properties; and (iii) inherent tendency to home to the areas of injury. The purpose of this study was to investigate the capacity of MSC to facilitate corneal epithelial regeneration, and the impact of corneal injury on homeostasis of endogenous MSC.
MSC were generated from the bone marrow of B6 mice, and were characterized phenotypically for expression of CD45CD34SCA1+CD29+, and functionally by differentiation into adipocytes. A mouse model of partial (50%) corneolimbal epithelial injury was created using thermocautery. MSC were labeled with red Q-Dot and then injected intravenously to one group of mice within 2h of corneal injury. Migration and homing of labeled MSC to the cornea were analyzed by epiflorescence microscopy. To measure the corneal epithelial regeneration, injured cornea were scored with corneal fluorescein staining using slit-lamp biomicroscopy. In addition, peripheral blood of mice was collected at 0, 24, 48 and 72 h post injury, and frequencies of endogenous MSC were analyzed by flow cytometry.
Intravenously injected Q-Dot labeled MSC were found primarily in the epithelium of the injured cornea, but not in the normal contralateral cornea. In addition, the epithelial injury group with MSC injection at 96h post injury showed a significant and rapid 3-fold decrease in corneal fluorescein staining compared to the group without MSC injection (p=0.015). Flow cytometric analysis of peripheral blood from mice with corneal injury showed a significant 2-fold increase in the frequencies of circulating CD45CD34SCA1+ endogenous MSC after 48h of corneal injury (p=0.005).
Our results clearly demonstrate that MSC have abilities to specifically home to injured cornea, and to promote corneal epithelial regeneration. In addition, our data suggest that injury to the corneal epithelium causes significant mobilization of endogenous MSC from bone marrow to blood.
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