Recent progress toward understanding the physiological function of bone marrow mesenchymal stem cells

Abstract

Mesenchymal stem cells (MSCs) are multipotent cells that are being clinically explored as regenerative therapeutics. Cultured MSCs secrete various modulatory factors, which contribute to the immunosuppressive effects of transplanted MSCs as a therapy. Although the in vitro phenotype of MSCs has been well characterized, identification of MSCs in vivo is made difficult by the lack of specific markers. Current advances in murine MSC research provide valuable tools for studying the localization and function of MSCs in vivo. Recent findings suggest that MSCs exert diverse functions depending on tissue context and physiological conditions. This review focuses on bone marrow MSCs and their roles in haematopoiesis and immune responses.

Figure 1

In vitro characteristics of mesenchymal stem cells (MSCs).

Figure 2

Cultured mesenchymal stem cells (MSCs) suppress the proliferation and activity of immune cells by secreting soluble factors. HGF, hepatocyte growth factor; IDO, indolamine dioxygenase; IL-10, interleukin-10; NK, natural killer; PGE₂, prostaglandin E₂; TGF-β, transforming growth factor-β.

Figure 3

Mesenchymal stem cells (MSCs) promote emigration of Ly6C^hi monocytes from the bone marrow following infection. MSC responds to circulating Toll-like receptor (TLR) ligands and secrete CCL2. Two models are proposed for the emigration of monocytes following CCL2 expression by MSCs. In the first model, CCL2 production in the bone marrow increases monocyte chemokinesis, thereby increasing the likelihood that monocytes will come into contact with blood vessels and subsequently cross the fenestrated endothelium. In the second model, CCL2 produced in proximity to vascular sinuses binds to glycosaminoglycans (GAGs) and forms a chemokine gradient, which attracts monocytes to the abluminal aspect of the endothelium and further guides their transmigration into the circulation. IFN, interferon.