Tolerance-like mediated suppression by mesenchymal stem cells in patients with dust mite allergy–induced asthma

Kapoor, Simi; Patel, Shyam A.; Kartan, Saritha; Axelrod, David E.; Capitle, Eugenio; Rameshwar, Pranela

doi:10.1016/j.jaci.2011.10.048

Cited by 52 publications

(50 citation statements)

References 45 publications

(56 reference statements)

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“…20 We also showed evidence of immune tolerance with repeated exposure of MSCs and allergen to the lymphocytes from subjects with allergic asthma. 20 Thus, we began this study by assuming that MSCs will suppress the antigen-challenged lymphocytes from AR subjects, without asthma. Our assumption was based on MSCs functioning as immune suppressor cells in an inflammatory milieu as noted for allergic asthma.…”

Section: Discussionmentioning

confidence: 62%

“…Furthermore, as we previously studied allergic asthma with dust mite, the section will answer if the effect of MSCs was antigen specific. 20 …”

Section: Resultsmentioning

confidence: 99%

“…These results, combined with our demonstration that CIITA knockdown decreased human leukocyte antigen (HLA)-DR expression (Figure 6a), confirmed the essential role of the APC functionality of MSCs in the observed effects on T-cell proliferation in the context of AR. 20 …”

Section: Resultsmentioning

confidence: 99%

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Pollen‐induced antigen presentation by mesenchymal stem cells and T cells from allergic rhinitis

Desai

Гаврилова

et al. 2013

Clin & Trans Imm

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Mesenchymal stem cells (MSCs) are promising cellular suppressor of inflammation. This function of MSCs is partly due to their licensing by inflammatory mediators. In cases with reduced inflammation, MSCs could become immune-enhancer cells. MSCs can suppress the inflammatory response of antigen-challenged lymphocytes from allergic asthma. Although allergic rhinitis (AR) is also an inflammatory response, it is unclear if MSCs can exert similar suppression. This study investigated the immune effects (suppressor vs enhancer) of MSCs on allergen-stimulated lymphocytes from AR subjects (grass or weed allergy). In contrast to subjects with allergic asthma, MSCs caused a significant (P<0.05) increase in the proliferation of antigen-challenged lymphocytes from AR subjects. The increase in lymphocyte proliferation was caused by the MSCs presenting the allergens to CD4+ T cells (antigen-presenting cells (APCs)). This correlated with increased production of inflammatory cytokines from T cells, and increased expressions of major histocompatibility complex (MHC)-II and CD86 on MSCs. The specificity of APC function was demonstrated in APC assay using MSCs that were knocked down for the master regulator of MHC-II transcription, CIITA. The difference in the effects of MSCs on allergic asthma and AR could not be explained by the sensitivity to the allergen, based on skin tests. Thus, we deduced that the contrasting immune effects of MSCs for antigen-challenged lymphocytes on AR and allergic asthma could be disease specific. It is possible that the enhanced inflammation from asthma might be required to license the MSCs to become suppressor cells. This study underscores the need for robust preclinical studies to effectively translate MSCs for any inflammatory disorder.

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Section: Discussionmentioning

confidence: 62%

“…Furthermore, as we previously studied allergic asthma with dust mite, the section will answer if the effect of MSCs was antigen specific. 20 …”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Pollen‐induced antigen presentation by mesenchymal stem cells and T cells from allergic rhinitis

Desai

Гаврилова

et al. 2013

Clin & Trans Imm

Self Cite

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“…The expansion of T-reg cells was likely due to the PGE 2 production by peripheral blood mononuclear cells and required cell-to-cell contact. In contrast, another study showed that the proliferation of peripheral blood mononuclear cells obtained from subjects with dust-mite allergic asthma was inhibited by allogeneic MSCs and was not associated with the induction of a CD25 + /CD4 + /Foxp3 + phenotype but rather with the blunting of DC maturation, associated with a significant increase in IL-10 levels [Kapoor et al, 2012].…”

Section: Immunomodulatory Effects Of Mscsmentioning

confidence: 91%

Paracrine Effects and Heterogeneity of Marrow-Derived Stem/Progenitor Cells: Relevance for the Treatment of Respiratory Diseases

Conese

Carbone

Castellani

et al. 2013

Cells Tissues Organs

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Stem cell-based treatment may represent a hope for the treatment of acute lung injury and pulmonary fibrosis, and other chronic lung diseases, such as cystic fibrosis, asthma and chronic obstructive pulmonary disease (COPD). It is well established in preclinical models that bone marrow-derived stem and progenitor cells exert beneficial effects on inflammation, immune responses and repairing of damage in virtually all lung-borne diseases. While it was initially thought that the positive outcome was due to a direct engraftment of these cells into the lung as endothelial and epithelial cells, paracrine factors are now considered the main mechanism through which stem and progenitor cells exert their therapeutic effect. This knowledge has led to the clinical use of marrow cells in pulmonary hypertension with endothelial progenitor cells (EPCs) and in COPD with mesenchymal stromal (stem) cells (MSCs). Bone marrow-derived stem cells, including hematopoietic stem/progenitor cells, MSCs, EPCs and fibrocytes, encompass a wide array of cell subsets with different capacities of engraftment and injured tissue-regenerating potential. The characterization/isolation of the stem cell subpopulations represents a major challenge to improve the efficacy of transplantation protocols used in regenerative medicine and applied to lung disorders.

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“…Cell proliferation was measured using tritiated thymidine ( 3 H-TdR) incorporation as described in Kapoor et al [35]. PBMCs were resuspended at 10 6 /mL in RPMI 640 (Sigma-Aldrich) and 10% fetal bovine serum (Hyclone; Thermo Fisher Scientific, Waltham, MA).…”

Section: Pbmc Proliferation Assaymentioning

confidence: 99%

Sodium Tungstate for Promoting Mesenchymal Stem Cell Chondrogenesis

Khader

Sherman

Rameshwar

et al. 2016

Stem Cells and Development

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Articular cartilage has a limited ability to heal. Mesenchymal stem cells (MSCs) derived from the bone marrow have shown promise as a cell type for cartilage regeneration strategies. In this study, sodium tungstate (Na 2 WO 4 ), which is an insulin mimetic, was evaluated for the first time as an inductive factor to enhance human MSC chondrogenesis. MSCs were seeded onto three-dimensional electrospun scaffolds in growth medium (GM), complete chondrogenic induction medium (CCM) containing insulin, and CCM without insulin. Na 2 WO 4 was added to the media leading to final concentrations of 0, 0.01, 0.1, and 1 mM. Chondrogenic differentiation was assessed by biochemical analyses, immunostaining, and gene expression. Cytotoxicity using human peripheral blood mononuclear cells (PBMCS) was also investigated. The chondrogenic differentiation of MSCs was enhanced in the presence of low concentrations of Na 2 WO 4 compared to control, without Na 2 WO 4 . In the induction medium containing insulin, cells in 0.01 mM Na 2 WO 4 produced significantly higher sulfated glycosaminoglycans, collagen type II, and chondrogenic gene expression than all other groups at day 28. Cells in 0.1 mM Na 2 WO 4 had significantly higher collagen II production and significantly higher sox-9 and aggrecan gene expression compared to control at day 28. Cells in GM and induction medium without insulin containing low concentrations of Na 2 WO 4 also expressed chondrogenic markers. Na 2 WO 4 did not stimulate PBMC proliferation or apoptosis. The results demonstrate that Na 2 WO 4 enhances chondrogenic differentiation of MSCs, does not have a toxic effect, and may be useful for MSC-based approaches for cartilage repair.

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Tolerance-like mediated suppression by mesenchymal stem cells in patients with dust mite allergy–induced asthma

Cited by 52 publications

References 45 publications

Pollen‐induced antigen presentation by mesenchymal stem cells and T cells from allergic rhinitis

Pollen‐induced antigen presentation by mesenchymal stem cells and T cells from allergic rhinitis

Paracrine Effects and Heterogeneity of Marrow-Derived Stem/Progenitor Cells: Relevance for the Treatment of Respiratory Diseases

Sodium Tungstate for Promoting Mesenchymal Stem Cell Chondrogenesis

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