P21supcip1/sup or p27supkip1/sup effects on the regulation of differentiation of human mesenchymal stem cells

摘要

Disclosed is a method for distinguishing undifferentiated human mesenchymal stem cells (hMSCs) from partially or completely differentiated human mesenchymal cells. In accordance with the invention it has been discovered that the expression of p21 Cyclin Inhibitor Protein (p21CIP1) is upregulated in partially or completely differentiated human mesenchymal cells as compared to undifferentiated hMSCs. Thus, this provides a quality control marker and test or assay to confirm that hMSCs are truly undifferentiated. That the p21CIP1 gene is either not expressed in clearly undifferentiated hMSCs or is significantly upregulated in partially or completely differentiated human mesenchymal cells by mesenchymal lineage inducers provides a screening method for identifying previously unknown mesenchymal lineage inducers. Also disclosed is an assay to determine the competence of mesenchymal progenitor cells to differentiate, particularly for in vivo tissue repair and particularly with respect to the osteogenic lineage. The inventors have made this possible by their observation that, in cells at approximately 80 % confluence in in vitro culture, p27 Kinase Inhibitor Protein (p27KIP1) expression levels are upregulated in differentiation competent mesenchymal stem cell as compared to differentiation incompetent mesenchymal stem cells.