Mesenchymal stromal cells: current understanding and clinical status

Abstract

Multipotent mesenchymal stromal cells (MSCs) represent a rare heterogeneous subset of pluripotent stromal cells that can be isolated from many different adult tissues that exhibit the potential to give rise to cells of diverse lineages. Numerous studies have reported beneficial effects of MSCs in tissue repair and regeneration. After culture expansion and in vivo administration, MSCs home to and engraft to injured tissues and modulate the inflammatory response through synergistic downregulation of proinflammatory cytokines and upregulation of both prosurvival and antiinflammatory factors. In addition, MSCs possess remarkable immunosuppressive properties, suppressing T-cell, NK cell functions, and also modulating dentritic cell activities. Tremendous progress has been made in preclinical studies using MSCs, including the ability to use allogeneic cells, which has driven the application of MSCs toward the clinical setting. This review highlights our current understanding into the biology of MSCs with particular emphasis on the cardiovascular and renal applications, and provides a brief update on the clinical status of MSC-based therapy.

Figure 1

Hierarchy of stem cells.

Figure 2

Proposed mechanisms involved in the homing and trafficking of mesenchymal stromal cells to sites of tissue injury after infusion. Abbreviations: ICAM, intercellular adhesion molecule; JAMs, junctional adhesion molecules; MSCs, mesenchymal stromal cells; PECAM, platelet-endothelial cell-adhesion molecule; PGE, prostaglandin E₂; VCAM, vascular cell-adhesion molecule; VLA, very late antigen.

Figure 3

Immunomodulation by mesenchymal stromal cells. Abbreviations: DCs, dentritic cells; HGF, hepatocyte growth factor; ICAM, intercellular adhesion molecule; IGF, insulin-like growth factor; IL, interleukin; JAMs, junctional adhesion molecules; MSCs, mesenchymal stromal cells; NK, natural killer; NO, nitric oxide; PD-1, programmed death one; PD-L1, programmed death one ligand; PGE₂ prostaglandin E₂; T-cell, T lymphocyte; TGFβ, transforming growth factor beta; TNFα, tumor necrosis factor-α; VEGF, vascular endothelial growth factor; VLA, very late antigen.