Molecular Profiles of Cell-to-Cell Variation in the Regenerative Potential of Mesenchymal Stromal Cells

Abstract

Cell-to-cell variation in the regenerative potential of mesenchymal stromal cells (MSCs) impedes the translation of MSC therapies into clinical practice. Cellular heterogeneity is ubiquitous across MSC cultures from different species and tissues. This review highlights advances to elucidate molecular profiles that identify cell subsets with specific regenerative properties in heterogeneous MSC cultures. Cell surface markers and global signatures are presented for proliferation and differentiation potential, as well as immunomodulation and trophic properties. Key knowledge gaps are discussed as potential areas of future research. Molecular profiles of MSC heterogeneity have the potential to enable unprecedented control over the regenerative potential of MSC therapies through the discovery of new molecular targets and as quality attributes to develop robust and reproducible biomanufacturing processes. These advances would have a positive impact on the nascent field of MSC therapeutics by accelerating the development of therapies with more consistent and effective treatment outcomes.

Figure 1

Applications of molecular profiles of MSC heterogeneity. Surface markers and global signatures identify cell subsets with specific regenerative properties in heterogeneous MSC cultures. Molecular profiles of MSC heterogeneity have application as molecular targets and quality attributes in the production of MSC therapeutics. Targeted molecules can be regulated by small-molecule and biologic pharmaceuticals, as well as by precision gene editing. Quality attributes enable enrichment of a MSC population and its assessment during all stages of biomanufacturing of MSC therapies from cell isolation to culture expansion to storage. This control over the composition and function of MSC therapies has the potential to improve treatment outcomes for patients.