Nomenclature and Heterogeneity: Consequences for the Use of Mesenchymal Stem Cells in Regenerative Medicine

Abstract

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.

Molecular and Functional Phenotypes of Human Bone Marrow-Derived Mesenchymal Stromal Cells Depend on Harvesting Techniques

“…To date, most studies describing clinical and histological healing after MSC application did not characterize MSC phenotypes via a combined proteomic/flow cytometric and functional approach [ 23 , 24 , 25 ]. Flow cytometric cell surface proteomics represents a powerful tool to describe cell surface epitopes and allows the correlation of specific markers with functional features of the analyzed cells.…”

A Small-Sized Population of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells Shows High Stemness Properties and Therapeutic Benefit

“…However, few studies have attempted to culture MSCs derived from a single cell or colony, and each original cell differs from each other [5][6][7]. Moreover, these obtained MSCs contain mixed populations exhibiting varying morphological features and gene expression patterns [8], which might imply that all cells are cultured in transitional culture environments. Recently, several groups have developed protocols to isolate more homogeneous cells from heterogeneous populations using specific antigens [9][10][11]; however, none of these processes have gained widespread acceptance, because there is no unique single marker.…”

Limited Potential or Unfavorable Manipulations? Strategies Toward Efficient Mesenchymal Stem/Stromal Cell Applications

“…While preclinical data on the efficacy of MSCs to treat pathological conditions are promising, translating this into clinical success is not straightforward. The cellular heterogeneity that is, on the one hand, an intrinsic property of cell communities-even in genetically identical cell populations (Wilson et al, 2019)-and on the other hand in case of clinically applied MSCs caused by the factors and parameters discussed above, might be one of the major reasons for the observed discrepancy in MSC efficacy (Galipeau and Sensebe, 2018). Despite these heterogeneities, how can we ensure that preclinical results hold true in clinical studies?…”