Purinergic receptors and nucleotide processing ectoenzymes: Their roles in regulating mesenchymal stem cell functions

Abstract

Human mesenchymal stem cells (MSCs) are a rare population of non-hematopoietic stem cells with multilineage potential, originally identified in the bone marrow. Due to the lack of a single specific marker, MSCs can be recognized and isolated by a series of features such as plastic adherence, a panel of surface markers, the clonogenic and the differentiation abilities. The recognized role of MSCs in the regulation of hemopoiesis, in cell-degeneration protection and in the homeostasis of mesodermal tissues through their differentiation properties, justifies the current interest in identifying the biochemical signals produced by MSCs and their active crosstalk in tissue environments. Only recently have extracellular nucleotides (eNTPs) and their metabolites been included among the molecular signals produced by MSCs. These molecules are active on both ionotropic and metabotropic receptors present in most cell types. MSCs possess a significant display of these receptors and of nucleotide processing ectoenzymes on their plasma membrane. Thus, from their niche, MSCs give a significant contribution to the complex signaling network of eNTPs and its derivatives. Recent studies have demonstrated the multifaceted aspects of eNTP metabolism and their signal transduction in MSCs and revealed important roles in specifying differentiation lineages and modulating MSC physiology and communication with other cells. This review discusses the roles of eNTPs, their receptors and ectoenzymes, and the relevance of the signaling network and MSC functions, and also focuses on the importance of this emerging area of interest for future MSC-based cell therapies.

Keywords: Mesenchymal stem cell; Purinergic receptors; Ectoenzymes; ATP; β-NAD; Adenosine; cADPR

Core tip: The multifaceted aspects of extracellular nucleotide metabolism (mainly ATP and β-NAD) on mesenchymal stem cell (MSC) surface has been addressed by basic researchers only recently, sometimes revealing unexpected pivotal roles for these molecules in specifying differentiation lineages and modulating MSC physiology and communication with other cells. This review discusses the roles of extracellular nucleotides, their receptors and ectoenzymes, and the relevance of their signaling network and MSC functions, and also focuses on the importance of this emerging area of interest for future MSC-based cell therapies.