Hierarchical therapeutic potential in the mesenchymal stem cell landscape

Le résumé fourni par la source

Mesenchymal stem cells (MSCs) are heterogeneous and versatile cells comprising distinct subpopulations with varying regenerative potential. MSCs have been widely explored in clinical research owing to their regenerative, tissue trophic, immune modulatory, and anti-inflammatory properties. Tissue-sourced autologous and allogeneic MSCs including those isolated from bone marrow, adipose tissue, and umbilical cord have been applied to clinical studies of a breadth of indications, providing ample evidence supporting the safety of MSC-based therapies. In some instances, clinical studies of MSCs have yielded variability in cell quality, potency, and therapeutic impact. Significantly, the Food and Drug Administration’s approval of the first MSC therapy, the allogeneic bone marrow MSC product Remestemcel-L-rknd (Ryoncil®), has fueled optimism for the clinical prospects of other investigational MSC products. The functional heterogeneity of MSCs has been demonstrated by studies of MSC subpopulations, often selected by surface marker expression or functional characteristics, that vary in clonogenicity, immunomodulatory potency, trophic factor production, and differentiation potential. While MSCs possess the ability to differentiate into mesodermal lineage cells, the potential for transdifferentiation of MSCs has been a matter of extensive scientific debate. There has been a strong impetus to identify MSC subpopulations that may possess enhanced self-renewal capabilities, higher clonogenicity, and greater plasticity. Certain MSC subpopulations, defined by specific surface markers or functional traits, have been reported to exhibit or enhanced therapeutic attributes compared to heterogeneous MSCs. Specific MSC subpopulations that have been examined include STRO-1 + cells, STRO-3-selected cells, CD146 + cells, CD271 + cells, aldehyde-dehydrogenase-expressing cells, side population (SP) cells, and stage-specific embryonic antigen-3 (SSEA-3) + cells. Due to the lack rigorous characterization of certain MSC subpopulations, their precise biological identities and the potential therapeutic advantages over heterogeneous MSCs remains to be fully defined. Here we review the preclinical and clinical advancements in the understanding of the therapeutic properties of MSCs and their subpopulations, assessing the evidence supporting their use in regenerative medicine.

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