Comparative gene expression analysis of corneal stroma mesenchymal stem cell-like cells, limbal epithelial stem cells and bone marrow-derived mesenchymal stem cells

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Abstract

Purpose

Purpose Stem cells in the central part of the cornea serve an important regenerative and homeostatic function. We aimed to describe the genetic fingerprint of these cells and compare that to limbal epithelial stem cells (LESC) and bone marrow-derived MSCs (bmMSCs).

Methods

Corneal tissue and bmMSCs were harvested from cadavers and healthy donors, respectively (according to the Guidelines of the Helsinki Declaration) and cultured ex vivo. MSC-specific cell surface markers- and genome-wide microarray analysis were performed using FACS and Affymetrix GeneChip Human Gene 1.0 ST Array (˜23,000 gene transcripts).

Results

Genes related to stemness (228), differentiation and lineage (220), cell cycle (108) and HOX, SOCS, Notch signaling (218) were collected into functional groups and clustered hierarchically: 45 genes were found to be specific for corneal stroma (CS)-MSCs, 62 for LESCs and 9 for bmMSCs. The hierarchical clustering clearly separated the CS-MSCs from the LESCs and bmMSCs, but formed a higher cluster with the later. The top 10 genes related to the differences were VCAM1, FNDC1, MFAP5, SFRP2, IGF2, MMP, ITGA2, COLEC12, SEMA3A and MGARP. Number of molecules functioning in cellular movement (381), cellular growth and proliferation (408), development (370) and cellular development (360) were found with top biological functions in CSMSCs compared to LESCs or bmMSCs (p<0.001).

Conclusion

Our data show clear distinction between the studied stem cells based upon their gene expression patterns and strengthen the hypothesis that CSMSCs are derived from bmMSCs and not from LESCs.

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