On the origin and impact of mesenchymal stem cell heterogeneity: new insights and emerging tools for single cell analysis

Abstract

Mesenchymal stem cells (MSCs) display substantial cell-to-cell variation. This heterogeneity manifests among donors, among tissue sources, and within cell populations. Such pervasive variability complicates the use of MSCs in regenerative applications and may limit their therapeutic efficacy. Most conventional assays measure MSC properties in bulk and, as a consequence, mask this cell-to-cell variation. Recent studies have identified extensive variability amongst and within clonal MSC populations, in dimensions including functional differentiation capacity, molecular state (e.g. epigenetic, transcriptomic, and proteomic status), and biophysical properties. While the origins of these variations remain to be elucidated, potential mechanisms include in vivo micro-anatomical heterogeneity, epigenetic bistability, and transcriptional fluctuations. Emerging tools for single cell analysis of MSC gene and protein expression may yield further insight into the mechanisms and implications of single cell variation amongst these cells, and ultimately improve the clinical utility of MSCs in tissue engineering and regenerative medicine applications. This review outlines the dimensions across which MSC heterogeneity is present, defines some of the known mechanisms that govern this heterogeneity, and highlights emerging technologies that may further refine our understanding and improve our clinical application of this unique cell type.

Human Skeletal Stem Cells: The Markers Provide Some Clues in the Hunt for Hidden Treasure

“…First identified in the bone marrow (as bone marrow mesenchymal stem cells, or BMMSCs), cells with similar properties have been identified in many other tissues, and ''MSC'' is considered an umbrella term to describe multipotent stem cells that give rise to multiple cell-type lineages (Bianco and Robey, 2015). However, these cell populations encompassing MSCs are heterogeneous (McLeod and Mauck, 2017), and their ability to differentiate into osteogenic progeny occurs with varying efficacies.…”

Cellular Spheroids of Mesenchymal Stem Cells and Their Perspectives in Future Healthcare

“…Therefore, for treating the specific disorders, the most suitable origin of MSCs has to be determined. Continuous improvement of biotechnology in the study of secretome, epigenetics, genomics, and proteomics is helpful for clarifying the differentiation and therapeutic capacities for MSCs derived from different origins [77]. To obtain a sufficient number of MSCs for medical applications, an appropriate expansion procedure is required.…”

Subpopulations of miniature pig mesenchymal stromal cells with different differentiation potentials differ in the expression of octamer-binding transcription factor 4 and sex determining region Y-box 2

“…However, other than their capacity to differentiate into specific lineages, no studies have fully characterized the features of these subpopulations. Identifying molecular markers for each subpopulation is important to increase the purity and uniformity of MSC pools [9].…”