Selected Stro‐1‐enriched bone marrow stromal cells display a major suppressive effect on lymphocyte proliferation

Abstract

Summary Mesenchymal stem cells (MSCs) have an immunosuppressive effect and can inhibit the proliferation of alloreactive T cells in vitro and in vivo. Cotransplantation of MSCs and hematopoietic stem cells (HSCs) from HLA‐identical siblings has been shown to reduce the incidence of acute graft‐vs.‐host disease. MSCs are heterogeneous and data on the inhibitory effects of different MSC subsets are lacking. The antigen Stro1 is a marker for a pure primitive MSC subset. We investigated whether Stro‐1‐enriched induce a more significant suppressive effect on lymphocytes in a mixed lymphocyte reaction (MLR), and whether this action is related to a specific gene expression profile in Stro‐1‐enriched compared to other MSCs. We demonstrated that the Stro‐1‐enriched population elicits a significantly more profound dose‐dependent inhibition of lymphocyte proliferation in a MLR than MSCs. One thousand expanded Stro‐1‐enriched induced an inhibitory effect comparable to that of 10 times as many MSCs. Inhibition by Stro‐1‐enriched was more significant in contact‐dependent cultures than in noncontact‐dependant cultures at higher ratio. The Stro‐1‐enriched inhibitory effect in both culture types was linked to increased gene expression for soluble inhibitory factors such as interleukin‐8 (IL‐8), leukemia inhibitory factor (LIF), indoleamine oxidase (IDO), human leukocyte antigen‐G (HLA‐G), and vascular cell adhesion molecule (VCAM1). However, tumor growth factor‐β1 (TGF‐β) and IL‐10 were only up‐regulated in contact‐dependant cultures. These results may support using a purified Stro‐1‐enriched population to augment the suppressive effect in allogeneic transplantation.

Human fallopian tube: a new source of multipotent adult mesenchymal stem cells discarded in surgical procedures

“…Although Nasef et al suggest that a purified Stro-1-enriched population augment the suppressive effect in allogeneic transplantation, Murphy et al showed that allogeneic endometrial regenerative cells (ERC or menstrual blood mesenchymal stem cells), that are Stro-1 negative, were efficient for the treatment of critical limb ischemia in rats [34,32]. In accordance to recent studies in human endometrium, htMSCs are also Stro1 negative [35].…”

Homing and migration of mesenchymal stromal cells: How to improve the efficacy of cell therapy?

“…Treatments with GSK-3β inhibitors and C1q also increase MMP expression in MSCs, which are important for the degradation of the basement membrane during extravasation [60,101] . A combination of the haematopoietic growth factors erythropoietin (EPO) and granulocyte colony stimulating factor (G-CSF) has also been reported Integrin αv [85] BM [85] Yes [85] Yes [85] Integrin β1 [11,[86][87][88] BM [11,[86][87][88] Yes [11,[86][87][88] CB [86,87] AT [86][87][88] Skin [87] Integrin β3 [85] BM [85] Yes [85] Yes [85] Integrin β4 [85] BM [85] Yes [85] Yes [85] ALCAM [17,87] BM [87] Yes [17] AT [87] CB [17,87] Proteases MMP-1 [90] BM [90] Yes [90] Yes [90] In vitro migration [90] MMP-2 [65,68,74,…”

“…There is great interest in using these cells in a wide variety of clinical domains, such as Neurology, Orthopaedics, Cardiology and Haematology [3][4][5][6] . This interest arises from the following MSC characteristics: They have immunomodulatory capacities, they are multipotent and are thus possible effectors for tissue regeneration, and they tend to migrate to sites of tissue injury/inflammation [7][8][9][10][11] . Additionally MSCs might escape immune recognition, although conflicting observations about this particular phenotype have been published.…”

The Main Molecules Involved in Human Mesenchymal Stem Cells Immunomodulation

“…One pathway by which TGFβ exerts its anti-proliferative effect on T lymphocytes is through blockade of the production of the T-cell mitogenic cytokine IL-2 [34]. TGFβ also inhibits cell proliferation through controlling the expression of cell cycle regulators, including up-regulation of cyclin-dependent kinase inhibitors (CKIs) p15, p21 and p27 and down-regulation of cell cycle-promoting factors, such as c-myc, cyclin D2 and cyclin E [35].…”