Corneal Mesenchymal Stromal Cells Are Directly Antiangiogenic via PEDF and sFLT-1
Rosenblatt, Mark I.
Djalilian, Ali R.
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CitationEslani, Medi, Ilham Putra, Xiang Shen, Judy Hamouie, Neda Afsharkhamseh, Soroush Besharat, Mark I. Rosenblatt, Reza Dana, Peiman Hematti, and Ali R. Djalilian. 2017. “Corneal Mesenchymal Stromal Cells Are Directly Antiangiogenic via PEDF and sFLT-1.” Investigative Ophthalmology & Visual Science 58 (12): 5507-5517. doi:10.1167/iovs.17-22680. http://dx.doi.org/10.1167/iovs.17-22680.
AbstractPurpose To evaluate the angiogenic properties of corneal derived mesenchymal stromal cells (Co-MSC). Methods: Co-MSCs were extracted from human cadaver, and wild-type (C57BL/6J) and SERPINF1−/− mice corneas. The MSC secretome was collected in a serum-free medium. Human umbilical vein endothelial cell (HUVEC) tube formation and fibrin gel bead assay (FIBA) sprout formation were used to assess the angiogenic properties of Co-MSC secretome. Complete corneal epithelial debridement was used to induce corneal neovascularization in wild-type mice. Co-MSCs embedded in fibrin gel was applied over the debrided cornea to evaluate the angiogenic effects of Co-MSCs in vivo. Immunoprecipitation was used to remove soluble fms-like tyrosine kinase-1 (sFLT-1) and pigment epithelium-derived factor (PEDF, SERPINF1 gene) from the Co-MSC secretome. Results: Co-MSC secretome significantly inhibited HUVECs tube and sprout formation. Co-MSCs from different donors consistently contained high levels of antiangiogenic factors including sFLT-1 and PEDF; and low levels of the angiogenic factor VEGF-A. In vivo, application of Co-MSCs to mouse corneas after injury prevented the development of corneal neovascularization. Removing PEDF or sFLT-1 from the secretome significantly diminished the antiangiogenic effects of Co-MSCs. Co-MSCs isolated from SERPINF1−/− mice had significantly reduced antiangiogenic effects compared to SERPINF1+/+ (wild-type) Co-MSCs. Conclusions: These results illustrate the direct antiangiogenic properties of Co-MSCs, the importance of sFLT-1 and PEDF, and their potential clinical application for preventing pathologic corneal neovascularization.
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