Osteodifferentiated Mesenchymal Stem Cells from Bone Marrow and Adipose Tissue Express HLA-G and Display Immunomodulatory Properties in HLA-Mismatched Settings: Implications in Bone Repair Therapy

Montespan, Florent; Deschaseaux, Frédéric; Sensebé, Luc; Carosella, Edgardo D.; Rouas‐Freiss, Nathalie

doi:10.1155/2014/230346

Cited by 59 publications

(52 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In fact, the suppressive effect was enhanced by ELCs in comparison with WJ‐MSCs and largely exerted under conditions of contact. Similar results were obtained after differentiation of MSCs into adipose, bone and cartilage lineages 14 , 15 , 47 . These results led us to investigate the effects of differentiated cells on: (1) a population of cells enriched in CD3 + T cells, the major effector cells of adaptive immunity; 48 and (2) NK cells, as they represent the major effector of the innate immune response exhibiting a critical role in early host defense against infections and cancer 49 …”

Section: Discussionsupporting

confidence: 64%

“…Similar results were obtained after differentiation of MSCs into adipose, bone and cartilage lineages. 14,15,47 These results led us to investigate the effects of differentiated cells on: (1) a population of cells enriched in CD3 + T cells, the major effector cells of adaptive immunity; 48 and (2) NK cells, as they represent the major effector of the innate immune response exhibiting a critical role in early host defense against infections and cancer. 49 We noticed that ELCs, and to a lesser extent WJ-MSCs, suppressed the proliferation of activated CD3 + T cells, mainly under cell-cell contact conditions.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Immunomodulation of endothelial differentiated mesenchymal stromal cells: impact on T and NK cells

et al. 2015

View full text Add to dashboard Cite

Wharton's jelly mesenchymal stromal cells (WJ-MSCs) are promising candidates for tissue engineering, as their immunomodulatory activity allows them to escape immune recognition and to suppress several immune cell functions. To date, however, few studies have investigated the effect of differentiation of the MSCs on this immunomodulation. To address this question, we sought to determine the impact of differentiation toward endothelial cells on immunoregulation by WJ-MSCs. Following differentiation, the endothelial-like cells (ELCs) were positive for CD31, vascular endothelial cadherin and vascular endothelial growth factor receptor 2, and able to take up acetylated low-density lipoproteins. The expression of HLA-DR and CD86, which contribute to MSCs immunoprivilege, was still weak after differentiation. We then co-cultured un- and differentiated MSCs with immune cells, under conditions of both direct and indirect contact. The proliferation and phenotype of the immune cells were analyzed and the mediators secreted by both ELCs and WJ-MSCs quantified. Interleukin (IL)-6, IL-1β, prostaglandin E2 and in particular indoleamine-2,3-dioxygenase expression were upregulated in ELCs on stimulation by T and NK cells, suggesting the possible involvement of these factors in allosuppression. ELCs co-cultured with T cells were able to generate CD25(+) T cells, which were shown to be of the CD4(+)CD25(+)FoxP3(+) regulatory subset. Direct contact between NK cells and ELCs or WJ-MSCs decreased the level of NK-activating receptor natural-killer group 2, member D. Moreover, direct co-culturing with ELCs stimulates CD73 acquisition on NK cells, a mechanism which may induce adenosine secretion by the cells and lead to an immunosuppressive function. Taken together, our results show that ELCs obtained following differentiation of WJ-MSCs remain largely immunosuppressive.

show abstract

Section: Discussionsupporting

confidence: 64%

Section: Discussionmentioning

confidence: 99%

Immunomodulation of endothelial differentiated mesenchymal stromal cells: impact on T and NK cells

et al. 2015

View full text Add to dashboard Cite

show abstract

“…15–17 Interestingly, fracture leads to suppression of the immune system, 18 with a local increase in the number of induced T regulatory (iT REG ) cells that suppress active adaptive immune responses within the fracture callus. 19 Studies have further shown that mesenchymal stem cells actively maintain a hypoimmunogenic state 20,21 through the production of immunosuppressive paracrine factors, 22–24 or through the direct actions of these cells on immune-cell populations, including T cells. 25,26 Such effects suggest that these cells impart immune tolerance throughout the early stages of endochondral bone formation and provide protection to the developing tissues by suppressing allo-proliferation of T cells during stem-cell recruitment and cartilage formation.…”

Section: Introductionmentioning

confidence: 99%

Fracture healing: mechanisms and interventions

2014

View full text Add to dashboard Cite

Fractures are the most common large-organ, traumatic injuries to humans. The repair of bone fractures is a postnatal regenerative process that recapitulates many of the ontological events of embryonic skeletal development. Although fracture repair usually restores the damaged skeletal organ to its pre-injury cellular composition, structure and biomechanical function, about 10% of fractures will not heal normally. This article reviews the developmental progression of fracture healing at the tissue, cellular and molecular levels. Innate and adaptive immune processes are discussed as a component of the injury response, as are environmental factors, such as the extent of injury to the bone and surrounding tissue, fixation and the contribution of vascular tissues. We also present strategies for fracture treatment that have been tested in animal models and in clinical trials or case series. The biophysical and biological basis of the molecular actions of various therapeutic approaches, including recombinant human bone morphogenetic proteins and parathyroid hormone therapy, are also discussed.

show abstract

“…]. For example, human bone marrow (BM)‐derived MSC have been reported to maintain their ability to suppress the proliferation of T cells from healthy individuals or rheumatoid arthritis (RA) patients following differentiation into osteoblasts or chrondocytes . Moreover, BMMSC‐derived chrondocytes reduced T‐cell activation and their ability to release proinflammatory mediators in vitro .…”

Section: Introductionmentioning

confidence: 99%

Adipogenic Differentiation of Mesenchymal Stem Cells Alters Their Immunomodulatory Properties in a Tissue-Specific Manner

Munir¹,

Ward

Sheriff³

et al. 2017

Stem Cells

View full text Add to dashboard Cite

Chronic inflammation is associated with formation of ectopic fat deposits that might represent damage‐induced aberrant mesenchymal stem cell (MSC) differentiation. Such deposits are associated with increased levels of inflammatory infiltrate and poor prognosis. Here we tested the hypothesis that differentiation from MSC to adipocytes in inflamed tissue might contribute to chronicity through loss of immunomodulatory function. We assessed the effects of adipogenic differentiation of MSC isolated from bone marrow or adipose tissue on their capacity to regulate neutrophil recruitment by endothelial cells and compared the differentiated cells to primary adipocytes from adipose tissue. Bone marrow derived MSC were immunosuppressive, inhibiting neutrophil recruitment to TNFα‐treated endothelial cells (EC), but MSC‐derived adipocytes were no longer able to suppress neutrophil adhesion. Changes in IL‐6 and TGFβ1 signalling appeared critical for the loss of the immunosuppressive phenotype. In contrast, native stromal cells, adipocytes derived from them, and mature adipocytes from adipose tissue were all immunoprotective. Thus disruption of normal tissue stroma homeostasis, as occurs in chronic inflammatory diseases, might drive “abnormal” adipogenesis which adversely influences the behavior of MSC and contributes to pathogenic recruitment of leukocytes. Interestingly, stromal cells programmed in native fat tissue retain an immunoprotective phenotype. Stem Cells 2017;35:1636–1646

show abstract

Osteodifferentiated Mesenchymal Stem Cells from Bone Marrow and Adipose Tissue Express HLA-G and Display Immunomodulatory Properties in HLA-Mismatched Settings: Implications in Bone Repair Therapy

Cited by 59 publications

References 23 publications

Immunomodulation of endothelial differentiated mesenchymal stromal cells: impact on T and NK cells

Immunomodulation of endothelial differentiated mesenchymal stromal cells: impact on T and NK cells

Fracture healing: mechanisms and interventions

Adipogenic Differentiation of Mesenchymal Stem Cells Alters Their Immunomodulatory Properties in a Tissue-Specific Manner

Contact Info

Product

Resources

About