Mesenchymal stem cells: Molecular characteristics and clinical applications

Abstract

Mesenchymal stem cells (MSCs) are non-hematopoietic stem cells with the capacity to differentiate into tissues of both mesenchymal and non-mesenchymal origin. MSCs can differentiate into osteoblastic, chondrogenic, and adipogenic lineages, although recent studies have demonstrated that MSCs are also able to differentiate into other lineages, including neuronal and cardiomyogenic lineages. Since their original isolation from the bone marrow, MSCs have been successfully harvested from many other tissues. Their ease of isolation and ex vivo expansion combined with their immunoprivileged nature has made these cells popular candidates for stem cell therapies. These cells have the potential to alter disease pathophysiology through many modalities including cytokine secretion, capacity to differentiate along various lineages, immune modulation and direct cell-cell interaction with diseased tissue. Here we first review basic features of MSC biology including MSC characteristics in culture, homing mechanisms, differentiation capabilities and immune modulation. We then highlight some in vivo and clinical evidence supporting the therapeutic roles of MSCs and their uses in orthopedic, autoimmune, and ischemic disorders.

Keywords: Autoimmune disease; Autologous transplant; Bone marrow stem cell; Cell-based therapy; Mesenchymal stem cells; Mesenchymal stromal cell; Therapeutic application.

Figure 1

Multipotential differentiation of mesenchymal stem cells. Mesenchymal stem cells (MSCs) are pluripotent progenitor cells with the capacity to differentiate into lineages of all three germ layers. The lineage-specific differentiation is a multi-stage and well-coordinated process controlled by key regulators. Runx2 and Osterix are important master regulators for osteogenic differentiation while peroxisome proliferator-activated receptor γ and CCAAT/enhancer binding protein β are important factors promoting adipogenesis. SRY-box 9 is the main regulator of chondrogenic regulation while MyoD plays a key role in myogenic differentiation. MSCs also have the ability, although to much lesser extent, to differentiate into other lineages, such as neuronal and cardiomyogenic cells (lighter arrows).