New insights into epithelial differentiation of human adipose-derived stem cells.

Although many studies using stem cells as therapeutic agents after renal failure have been published in recent years, our knowledge of the factors involved and the cellular mechanisms underlying their beneficial effect on organ regeneration is incomplete. A growing insight into these interactions would help to utilize the biological potential of stem cells for therapeutic approaches. It is here hypothesized that soluble factors released by tubular epithelial cells (TECs) induce epithelial differentiation in adipose-derived adult mesenchymal stem cells (ASCs). ASCs were therefore cultured in conditioned medium (CM) derived from TECs and the changes in expression genes towards an epithelial pattern were determined by microarray and qPCR analyses. The changes in gene expression were evaluated using Affymetrix HG-U133 Plus 2.0 arrays. Microarray-based screening revealed 117 genes differentially expressed in a significant manner after short-time incubation (3 days) of ASCs with CM, and four of these were solute carriers (SLCs). Changes in mRNA expression of these SLCs were verified by qPCR at several time points, additionally with four stem cell factors and five epithelial markers. qPCR analyses showed that expression of three of the SLCs rose significantly, whereas three of the four stem cell markers analysed decreased during 7 days of CM incubation. Moreover, a robust expression of three characteristic epithelial markers (cytokeratin 18, ZO-1 and ZO-2) was observed after 17 days. These changes in the expression patterns strongly indicate differentiation towards the epithelial lineage. The capability of ASCs to differentiate into epithelial cells may be important in organ repair mechanisms.