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Purinergic Receptors Influence the Differentiation of Human Mesenchymal Stem Cells

  • Adult stem cells, including adipose tissue-derived mesenchymal stem cells (MSCs) or ectomesenchymal dental follicle cells (DFCs), attract considerable attention for their potential to differentiate into lineages, which are of major interest in the field of Regenerative Medicine. Purinergic receptors exert a wide range of biological actions in many cell and tissue types through extracellular nucleotides. Little is known about P2 receptors in adult stem cells and changes in their expression levels during differentiation. All known P2 receptors have been investigated, and a variety of P2X and P2Y receptor subtypes were detected in MSCs. Studies investigating intracellular calcium levels on receptor stimulation demonstrated that the found P2 receptors are metabolically active. Interestingly, up- or downregulation of several P2 receptor subtypes at gene and protein level was observed during adipogenic and osteogenic differentiation, and the effect on differentiation was directly influenced by both the application of agonists/antagonists and apyrase-induced nucleotide cleavage. Here, we show for the first time that the combination of several P2 receptors plays a role in the differentiation of adult stem cells. The expression pattern of the P2 receptors, as well as their fate in differentiation, varies in stem cells of mesenchymal origin if compared with stem cells of ectomesenchymal origin. The subtypes P2X6, P2Y4, and P2Y14 seem to be pivotal regulators in MSC commitment, as they are regulated in both adipogenic and osteogenic differentiation of adipose tissue-derived stem cells and DFCs. These findings provide new insights into the differentiation processes and might reveal novel options to influence stem cell fate in future applications.

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Document Type:Article
Author:Nina Zippel, Christian Andreas Limbach, Nadine Ratajski, Christian Urban, Claudio Luparello, Andreas Pansky, Matthias Ullrich Kassack, Edda Tobiasch
Parent Title (English):Stem Cells and Development
First Page:884
Last Page:900
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=21740266
Date of first publication:2011/07/08
The work was supported by BMBF, AdiPaD, 1720X06; Geräteprogramm, Fachhochschulen NRW 2008 and by HIFF, Fördergesellschaft der Fachhochschule Bonn-Rhein-Sieg for E.T. and University of Palermo, R.S. ex60% for C.L. and DAAD, PPP Vigoni, D/07/13409 for E.T. and C.L.
Tag:Adult Stem Cells/physiology; Cell Differentiation/physiology; Gene Expression Regulation; Humans; Mesenchymal Stromal Cells/cytology; Receptors, Purinergic P2; Receptors, Purinergic/genetics/physiology
Departments, institutes and facilities:Fachbereich Angewandte Naturwissenschaften
Dewey Decimal Classification (DDC):6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Entry in this database:2015/04/02