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Chapter 99 Mesenchymal Stromal Cells 1561

CD105 CD45 CD34

Cell Counts CD73 CD11b CD19

CD90 CD3 HLA-DR

Log Fluorescence Intensity
MSCs

Osteoblasts Adipocytes Chondroblasts

Fig. 99.2 A PANEL OF DATA DEMONSTRATING THE DEFINING CHARACTERISTICS OF
MESENCHYMAL STROMAL CELLS: ADHERENCE, IMMUNOPHENOTYPE, AND IN VITRO
DIFFERENTIATION. Top left, photomicrograph of undifferentiated MSCs showing the characteristic spindle
shape and adherent properties of the cells. Original magnification, ×40. Top right, flow cytometry histograms
demonstrating the typical expression pattern of surface antigens (blue line) and isotype control (red line), as
indicated. Bottom, immunocytochemical staining demonstrating the differentiation of MSCs into osteoblasts
(Alizarin Red stain), adipocytes (Oil Red O stain), and chondroblasts (Alcian Blue stain). MSC, Mesenchymal
stem cell. (With permission from Martinez C, Hofmann TJ, Marino R, et al: Human bone marrow mesenchymal stromal
cells express the neural ganglioside GD2: A novel surface marker for the identification of MSCs. Blood 109:4245, 2007.)

role of these molecules in MSCs has not been established. However, chemoattractant for a variety of cells, in particular hematopoietic
CD73, an ectoenzyme that catalyzes the dephosphorylation of ade- stem/progenitor cells. It supports the function of MSCs in HSC
nosine monophosphates into adenosine, is known to suppress adap- niches and tissue regeneration. The role of CXCL-12 in the immune
tive immune responses. MSCs constitutively express major properties of MSC has not been fully investigated; however, while
histocompatibility complex (MHC) class I molecules and are able to this cytokine has been described to mediate attraction and prolifera-
present MHC class I-restricted epitopes from transfected tumor tion of lymphocytes, it may also favor the establishment of immune
+
antigens or virally introduced antigens to CD8 T lymphocytes. It tolerance in vivo. IL-6 is a well-characterized cytokine that functions
has been demonstrated that human MSCs are capable of cross- in inflammation, lymphocyte proliferation, and B-cell maturation.
presentation of soluble antigens and effective antigenic presentation Compared with primary blood macrophages, basal production of
+
to naive CD8 T cells. Expression of CD80, CD86, CD28, ICOSL, IL-6 and PGE 2 is substantial in MSCs. For instance, primary
6
and 41BBL co-stimulatory molecules are not observed on MSCs; unstimulated human macrophages produce less than 1 ng/48 h/10
6
however, they express low levels of CD54/ICAM-1 or CD106/ cells of IL-6, while human MSCs produce 5–30 ng/48 h/10 cells of
VCAM-1, both of which could play a role in T-cell co-stimulation. IL-6, and production of PGE 2 and IL-6 by MSCs is increased upon
MSCs have been shown to produce basal levels of biologically active exposure to inflammatory products, such as tumor necrosis factor-α
chemokines, cytokines, and inflammatory mediators, in particular (TNF-α) or Toll-like receptor (TLR) ligands. Accordingly, inhibition
CXC-chemokine ligand 12 (CXCL-12)/SDF-1, IL-6, prostaglandin of IL-6 produced by MSCs results in enhanced suppression of pro-
E2 (PGE 2), and TGF-β. CXCL-12 is a small chemotactic cytokine liferation of activated lymphocytes in vitro. IL-6 was shown to be
that is often found in inflammatory sites and is an important responsible for neutrophil protection from apoptosis in cultures with