Nomenclature and heterogeneity: consequences for the use of mesenchymal stem cells in regenerative medicine

Mesenchymal stem cells (MSCs) are in development for many clinical indications, based both on stem' properties (tissue repair or regeneration) and on signaling repertoire (immunomodulatory and anti-inflammatory effects). Potential conflation of MSC properties with those of tissue-derived stromal cells presents difficulties in comparing study outcomes and represents a source of confusion in cell therapy development. Cultured MSCs demonstrate significant heterogeneity in clonogenicity and multi-lineage differentiation potential. However in vivo biology of MSCs includes native functions unrelated to regenerative medicine applications, so do nomenclature and heterogeneity matter? In this perspective we examine some consequences of the nomenclature debate and heterogeneity of MSCs. Regulatory expectations are considered, emphasizing that product development should prioritize detailed characterization of therapeutic cell populations for specific indications.