Limits...
Are mesenchymal stromal cells immune cells?

Hoogduijn MJ - Arthritis Res. Ther. (2015)

Bottom Line: Although originally identified as precursor cells for mesenchymal lineages, in vitro studies have demonstrated that MSCs possess diverse immune regulatory capacities.Correct understanding of the immunological properties and origin of MSCs will aid in the appropriate and safe use of the cells for clinical therapy.In this review the whole spectrum of immunological properties of MSCs is discussed with the aim of determining the position of MSCs in the immune system.

View Article: PubMed Central - PubMed

Affiliation: Nephrology and Transplantation, Department of Internal Medicine, Erasmus MC, 3000, CA, Rotterdam, the Netherlands. m.hoogduijn@erasmusmc.nl.

ABSTRACT
Mesenchymal stromal cells (MSCs) are considered to be promising agents for the treatment of immunological disease. Although originally identified as precursor cells for mesenchymal lineages, in vitro studies have demonstrated that MSCs possess diverse immune regulatory capacities. Pre-clinical models have shown beneficial effects of MSCs in multiple immunological diseases and a number of phase 1/2 clinical trials carried out so far have reported signs of immune modulation after MSC infusion. These data indicate that MSCs play a central role in the immune response. This raises the academic question whether MSCs are immune cells or whether they are tissue precursor cells with immunoregulatory capacity. Correct understanding of the immunological properties and origin of MSCs will aid in the appropriate and safe use of the cells for clinical therapy. In this review the whole spectrum of immunological properties of MSCs is discussed with the aim of determining the position of MSCs in the immune system.

Show MeSH

Related in: MedlinePlus

Overview of the interactions between mesenchymal stromal cells (MSCs) and immune cells. MSCs secrete cytokines (including transforming growth factor β, hepatocyte growth factor, IL-6, IL-7), chemokines (CCL2, IL-8) and prostaglandins (prostaglandin-E2), and express proliferation inhibitory cell surface molecules (programmed death ligand 1, Fas ligand) and metabolic enzymes (indoleamine 2,3-dioxygenase, CD73) that target immune cells in various ways. APC, antigen-presenting cell; NK, natural killer; TLR, Toll-like receptor.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC4377851&req=5

Fig1: Overview of the interactions between mesenchymal stromal cells (MSCs) and immune cells. MSCs secrete cytokines (including transforming growth factor β, hepatocyte growth factor, IL-6, IL-7), chemokines (CCL2, IL-8) and prostaglandins (prostaglandin-E2), and express proliferation inhibitory cell surface molecules (programmed death ligand 1, Fas ligand) and metabolic enzymes (indoleamine 2,3-dioxygenase, CD73) that target immune cells in various ways. APC, antigen-presenting cell; NK, natural killer; TLR, Toll-like receptor.

Mentions: MSCs interact with cells of the immune system via a plethora of mechanisms. They secrete anti-inflammatory factors such as transforming growth factor β (TGF-β), hepatocyte growth factor (HGF) and prostaglandin-E2 (PGE-2) [7,8], and they express cell surface molecules with immunosuppressive properties such as programmed death ligand 1 (PD-L1) and Fas ligand [15,16], via which they directly target immune cells and inhibit their activation and function. MSCs furthermore attract immune cells by secreting a broad mixture of chemokines. In particular, the neutrophil chemo-attractant interleukin (IL)-8 and the monocyte-attractant CCL2 are secreted in high amounts by MSCs [17]. Chemokine secretion by MSCs may act in a dual way to modulate the immune response. Reactive immune cells will be attracted and exert their immunological function, but at the same time they may be targeted by MSCs and inhibited in their function. There is evidence that MSCs bind activated immune cells [18], potentially to keep them at a close distance to enhance the effect of their immunosuppressive actions. The immunoregulatory effects of MSCs are not only directed directly against efxfector immune cells. MSCs do not themselves produce the anti-inflammatory cytokine IL-10, but they induce other cell types to do this [19]. Via the secretion of TGF-β and other factors MSCs also promote the induction of regulatory T cells [20], regulatory macrophages [21] and regulatory B cells [22], and in this way pass on their immunosuppressive effects to other cell types that exert different mechanisms of immune suppression. A schematic overview of the interactions between MSCs and immune cells is depicted in Figure 1.Figure 1


Are mesenchymal stromal cells immune cells?

Hoogduijn MJ - Arthritis Res. Ther. (2015)

Overview of the interactions between mesenchymal stromal cells (MSCs) and immune cells. MSCs secrete cytokines (including transforming growth factor β, hepatocyte growth factor, IL-6, IL-7), chemokines (CCL2, IL-8) and prostaglandins (prostaglandin-E2), and express proliferation inhibitory cell surface molecules (programmed death ligand 1, Fas ligand) and metabolic enzymes (indoleamine 2,3-dioxygenase, CD73) that target immune cells in various ways. APC, antigen-presenting cell; NK, natural killer; TLR, Toll-like receptor.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4377851&req=5

Fig1: Overview of the interactions between mesenchymal stromal cells (MSCs) and immune cells. MSCs secrete cytokines (including transforming growth factor β, hepatocyte growth factor, IL-6, IL-7), chemokines (CCL2, IL-8) and prostaglandins (prostaglandin-E2), and express proliferation inhibitory cell surface molecules (programmed death ligand 1, Fas ligand) and metabolic enzymes (indoleamine 2,3-dioxygenase, CD73) that target immune cells in various ways. APC, antigen-presenting cell; NK, natural killer; TLR, Toll-like receptor.
Mentions: MSCs interact with cells of the immune system via a plethora of mechanisms. They secrete anti-inflammatory factors such as transforming growth factor β (TGF-β), hepatocyte growth factor (HGF) and prostaglandin-E2 (PGE-2) [7,8], and they express cell surface molecules with immunosuppressive properties such as programmed death ligand 1 (PD-L1) and Fas ligand [15,16], via which they directly target immune cells and inhibit their activation and function. MSCs furthermore attract immune cells by secreting a broad mixture of chemokines. In particular, the neutrophil chemo-attractant interleukin (IL)-8 and the monocyte-attractant CCL2 are secreted in high amounts by MSCs [17]. Chemokine secretion by MSCs may act in a dual way to modulate the immune response. Reactive immune cells will be attracted and exert their immunological function, but at the same time they may be targeted by MSCs and inhibited in their function. There is evidence that MSCs bind activated immune cells [18], potentially to keep them at a close distance to enhance the effect of their immunosuppressive actions. The immunoregulatory effects of MSCs are not only directed directly against efxfector immune cells. MSCs do not themselves produce the anti-inflammatory cytokine IL-10, but they induce other cell types to do this [19]. Via the secretion of TGF-β and other factors MSCs also promote the induction of regulatory T cells [20], regulatory macrophages [21] and regulatory B cells [22], and in this way pass on their immunosuppressive effects to other cell types that exert different mechanisms of immune suppression. A schematic overview of the interactions between MSCs and immune cells is depicted in Figure 1.Figure 1

Bottom Line: Although originally identified as precursor cells for mesenchymal lineages, in vitro studies have demonstrated that MSCs possess diverse immune regulatory capacities.Correct understanding of the immunological properties and origin of MSCs will aid in the appropriate and safe use of the cells for clinical therapy.In this review the whole spectrum of immunological properties of MSCs is discussed with the aim of determining the position of MSCs in the immune system.

View Article: PubMed Central - PubMed

Affiliation: Nephrology and Transplantation, Department of Internal Medicine, Erasmus MC, 3000, CA, Rotterdam, the Netherlands. m.hoogduijn@erasmusmc.nl.

ABSTRACT
Mesenchymal stromal cells (MSCs) are considered to be promising agents for the treatment of immunological disease. Although originally identified as precursor cells for mesenchymal lineages, in vitro studies have demonstrated that MSCs possess diverse immune regulatory capacities. Pre-clinical models have shown beneficial effects of MSCs in multiple immunological diseases and a number of phase 1/2 clinical trials carried out so far have reported signs of immune modulation after MSC infusion. These data indicate that MSCs play a central role in the immune response. This raises the academic question whether MSCs are immune cells or whether they are tissue precursor cells with immunoregulatory capacity. Correct understanding of the immunological properties and origin of MSCs will aid in the appropriate and safe use of the cells for clinical therapy. In this review the whole spectrum of immunological properties of MSCs is discussed with the aim of determining the position of MSCs in the immune system.

Show MeSH
Related in: MedlinePlus