Challenges Toward the Identification of Predictive Markers for Human Mesenchymal Stromal Cells Chondrogenic Potential

Human bone marrow derived mesenchymal stromal cells (BMSCs) represent a putative cell source candidate for tissue engineering-based strategies to repair cartilage and bone. However, traditional isolation of BMSCs by adhesion to plastic leads to very heterogeneous cell populations, accounting for high variability of chondrogenic differentiation outcome, both across donors and across clonally derived strains. Identification of putative surface markers able to select BMSC subpopulations with higher chondrogenic capacity (CC) and reduced variance in chondrogenic differentiation could aid the development of BMSC-based cartilage and bone regeneration approaches. With the goal to identify predictive markers for chondrogenic BMSC populations, we assessed the gene expression profile of single cell-derived clones with high and low CC. While a clustering between high and low CC clones was observed for one donor, donor-to-donor variability hampered the possibility to achieve conclusive results when different donors were considered. Nevertheless, increased NCAM1/CD56 expression correlated in clones derived from one donor with higher CC, the same trend was observed for three additional donors (even if no significance was achieved). Enriching multiclonal BMSCs for CD56⁺ expression led to an increase in CC, though still highly affected by donor-to-donor variability. Our study finally suggests that definition of predictive marker(s) for BMSCs chondrogenesis is challenged by the large donor heterogeneity of these cells, and by the high complexity and plasticity of the BMSCs system. Multiple pathways and external parameters may be indeed involved in determining the chondrogenic potential of BMSCs, making the identification of putative markers still an open issue. Stem Cells Translational Medicine 2019;8:194&11.