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J. Oh, H. Choi, D.-K. Kim, R.-H. Lee, K. Claypool, B. Larson, G. Roddy, D. Prockop; Soluble Factors From Adult Stem/Progenitor Cells (MSCs) Protect Corneal Epithelial Progenitors by Promoting Proliferation and Preventing Apoptosis. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3743.
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Recent reports have demonstrated that adult stem/progenitor cells from bone marrow (multipotent mesenchymal stem cells; MSCs) frequently repair injured tissues without much evidence of either engraftment or differentiation. Instead, the beneficial effects in some disease models are explained by MSCs being activated by injured tissues to produce factors that are anti-inflammatory, immunomodulatory or anti-apoptotic. In view of these observations, we hypothesized that soluble factors from MSCs might have therapeutic effects in corneal surface disease.
To test the hypothesis, we incubated human corneal epithelial progenitor cells (hCEPs) for 48 hr (a) with or without prior injury by brief exposure to ethanol and (b) with or without conditioned media from standard cultures of human MSCs (hMSCs) or conditioned media from hMSCs that were pre-activated to express therapeutic factors by incubation with TNF-α for 24 hr. Both fresh media and the media conditioned from cultures of human dermal fibroblasts were used as controls. After incubation, we evaluated the cell viability, proliferation, and apoptosis in hCEPs.
We found that conditioned media from hMSCs or from pre-activated hMSCs significantly increased the viability and promoted the proliferation of both non-injured and injured hCEPs. Also, the apoptosis of hCEPs was inhibited significantly by conditioned media from pre-activated hMSCs. The proportion of the cells expressing progenitor markers were higher in injured corneal epithelial cells treated with MSC-conditioned media, compared to control-treated cells.
Our data collectively suggest that MSC-derived factors can protect the corneal surface from injury by controlling the proliferation, differentiation, and apoptosis of corneal epithelial progenitors.
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