Mesenchymal stem cells: revisiting history, concepts, and assays

Abstract

The concept of mesenchymal stem cells has gained wide popularity. Despite the rapid growth of the field, uncertainties remain with respect to the defining characteristics of these cells, including their potency and self-renewal. These uncertainties are reflected in a growing tendency to question the very use of the term. This commentary revisits the experimental origin of the concept of the population(s) referred to as mesenchymal stem cells and the experimental framework required to assess their stemness and function.

Figure 1. Model Proposing that Pericytes Serve as a Reservoir of Tissue-Specific Progenitors

The recruitment of local tissue progenitors as mural cells/pericytes in different tissues such as bone marrow and skeletal muscle is depicted. (A) During development, local osteogenic cells (osteoblasts, left side) in the BM associate with the vascular wall as subendothelial mural cells/ pericytes (adventitial reticular cells in sinusoids). In the postnatal organ, these cells can be explanted and assayed as clonogenic skeletal progenitors (bone, right side). (B) Blood vessels assoc iate with local myogenic progenitors in developing muscle, which are recruited into being pericytes (myocytes, left side). Consequently, pericytes isolated from the microvasculature of skeletal muscle will exhibit myogenic potential (muscle, right side). Therefore, this model predicts that although pericytes in different connective tissues may arise by a common developmental pathway and share anatomic identity, their differentiation capacity is likely to be tissue specific.