The importance of drug transporters in human pluripotent stem cells and in early tissue differentiation

Expert Opin Drug Metab Toxicol. 2016;12(1):77-92. doi: 10.1517/17425255.2016.1121382. Epub 2015 Dec 14.

Abstract

Introduction: Drug transporters are large transmembrane proteins which catalyse the movement of a wide variety of chemicals, including drugs as well as xeno- and endobiotics through cellular membranes. The major groups of these proteins include the ATP-binding cassette transporters which in eukaryotes work as ATP-fuelled drug 'exporters' and the Solute Carrier transporters, with various transport directions and mechanisms.

Areas covered: In this review, we discuss the key ATP-binding cassette and Solute Carrier drug transporters which have been reported to contribute to the function and/or protection of undifferentiated human stem cells and during tissue differentiation. We review the various techniques for studying transporter expression and function in stem cells, and the role of drug transporters in foetal and placental tissues is also discussed. We especially focus on the regulation of transporter expression by factors modulating cell differentiation properties and on the function of the transporters in adjustment to environmental challenges.

Expert opinion: The relatively new and as yet unexplored territory of transporters in stem cell biology may rapidly expand and bring important new information regarding the metabolic and epigenetic regulation of 'stemness' and the early differentiation properties. Drug transporters are clearly important protective and regulatory components in stem cells and differentiation.

Keywords: ABC transporters; SLC transporters; drug transporters; human stem cell differentiation; pluripotent stem cells; regulation of transporter expression.

Publication types

  • Review

MeSH terms

  • ATP-Binding Cassette Transporters / metabolism*
  • Animals
  • Biological Transport / physiology
  • Cell Differentiation / physiology
  • Cell Membrane / metabolism
  • Epigenesis, Genetic
  • Humans
  • Membrane Transport Proteins / metabolism*
  • Pluripotent Stem Cells / cytology
  • Pluripotent Stem Cells / metabolism*
  • Xenobiotics / pharmacokinetics

Substances

  • ATP-Binding Cassette Transporters
  • Membrane Transport Proteins
  • Xenobiotics