Adult mesenchymal stem/progenitor cells (MSCs) derived from numerous tissues are receiving ever-increasing attention as potential cellular sources for the development of regenerative medicine-based therapies against a wide range of diseases and conditions. Such basic science and translational research focus has grown based on the established self-renewal, clonogenic, multi-potency, anti-inflammatory, and immunomodulatory properties of MSCs, which make them ideal candidates for regenerative medicine purposes.

However, although methodologies exist enabling the routine isolation of MSCs from tissues for experimental applications and therapy development, a significant issue which still surrounds the translational development of MSC-based therapies is the acknowledged heterogeneous nature of MSC populations, resulting from MSCs within tissues being collectively comprised of many individual sub-populations with contrasting biological characteristics and regenerative potentials. Thus, a remaining challenge to regenerative medicine is the identification of particular molecular markers capable of discriminating MSCs with superior properties, versus lesser quality sub-populations. By overcoming these MSC heterogeneity issues through the identification and validation of specific molecular traits, these may be subsequently be exploited for the development of strategies enabling the selective screening, identification, and isolation of more potent MSC sub-populations with superior phenotypic properties from tissues. Such developments would subsequently allow more efficient assessment, therapy development, and banking, thereby aiding the translational development of more effective MSC-based therapies for clinical use in the future.

This Special Issue invites contributions focusing on the developmental origins and roles of stem cell niches on MSC heterogeneity within tissues. The Issue also incorporates recent advances made in the identification and utilization of particularly novel cell surface, gene, protein, or metabolic markers and techniques, which distinguish between MSC sub-populations with contrasting phenotypes, such as proliferative, differentiation, anti-inflammatory, or immunosuppressive capabilities; or which demonstrate superior tissue regeneration properties in vitro or in vivo. The potential use of such high quality MSC sub-populations for the treatment of common immuno-inflammatory and age-related conditions will further meet the remit of this Issue. Original research and review articles are welcome.

Potential topics include but are not limited to the following:

• The developmental basis underlying the existence of MSC heterogeneity within tissues and organs
• The role of stem cell niches as a source of MSC heterogeneity within tissues and organs
• Identification and characterization of novel cell surface and other gene, protein, or metabolic markers to distinguish between MSC sub-populations with contrasting phenotypic capabilities
• Cell surface or other gene, protein, and metabolic marker characteristics correlating to superior anti-inflammatory properties in particular MSC sub-populations
• Cell surface or other gene, protein, and metabolic marker characteristics correlating to superior immuno-modulatory properties in particular MSC sub-populations
• Cell surface or other gene, protein, and metabolic marker characteristics correlating to superior proliferative or resistance to senescence capabilities in particular MSC sub-populations
• Cell surface or other gene, protein, and metabolic marker characteristics correlating to superior multi-potency or regenerative capabilities in particular MSC sub-populations
• Novel isolation and characterization protocols or techniques developed to selectively screen, identify, and isolate particular MSC sub-populations from tissues using specific cell markers