The Response of Breast Cancer Cells to Mesenchymal Stem Cells

Orciani, Monia; Lazzarini, Raffaella; Scartozzi, Mario; Bolletta, Elisa; Mattioli‐Belmonte, Monica; Scalise, Alessandro; Benedetto, Giovanni Di; Primio, Roberto Di

doi:10.1097/01.prs.0000434401.98939.60

Cited by 19 publications

(10 citation statements)

References 30 publications

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“…Our previous studies confirm that the higher expression of TNF‐α in the microenvironment of psoriasis skin influences MSCs in psoriasis, and MSCs obtained from skin of patients with psoriasis are early committed towards a psoriatic phenotype . In particular, the imbalance between the Th 1 /Th 17 and Th 2 axes, previously observed in differentiated cells of psoriasis skin lesions, is resident also in MSCs .…”

Section: Discussionsupporting

confidence: 88%

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TNF‐α inhibitors reduce the pathological Th₁–Th₁₇/Th₂ imbalance in cutaneous mesenchymal stem cells of psoriasis patients

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Orciani

Lazzarini

et al. 2016

Experimental Dermatology

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Psoriasis is a disease characterized by an imbalance between Th and Th and Th inflammatory axes, in which cutaneous mesenchymal stem cells (MSCs) are early involved, as they show a greater relative expression of several genes encoding for Th and Th cytokines. Therapeutic implications of TNF-α inhibitors on differentiated skin cells have been largely described in psoriasis; however, their effects on MSCs derived from patients with psoriasis have been only partially described. The aim of this work was to evaluate the effect of TNF-α inhibitors on cytokine milieu expressed by MSCs isolated from the skin of patients with psoriasis. Resident MSCs from skin of patients with psoriasis and healthy subjects have been isolated, characterized and profiled by PCR and ELISA for the expression of 22 cytokines involved in Th , Th and Th pathways, both before and after 12 weeks therapy with TNF-α inhibitors. The administration of TNF-α inhibitors for 12-weeks acts on MSCs as follows: it reduces the expression of several Th -Th cytokines whose levels are elevated at baseline (IL-6, IL-8, IL-12, IL-23A, IFN-γ, TNF-α, CCL2, CCL20, CXCL2, CXCL5, IL-17A, IL-17C, IL-17F, IL-21, G-CSF). Similarly, it enhances the expression of several Th cytokines which are underexpressed at baseline (IL-2, IL-4, IL-5), reducing the expression of those overexpressed at baseline (TGF-β and IL-13). TNF-α inhibitors could contribute to reduce the pathological imbalance between the Th -Th vs Th axis in MSCs of patients with psoriasis.

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Section: Discussionsupporting

confidence: 88%

“…Many studies have found that MSCs possess immunoregulatory capabilities . The immunosuppressive ability of MSCs has been studied both in vitro and in vivo over the last few years, but the detailed mechanisms of their immunosuppression remain controversial .…”

Section: Discussionmentioning

confidence: 99%

TNF‐α inhibitors reduce the pathological Th₁–Th₁₇/Th₂ imbalance in cutaneous mesenchymal stem cells of psoriasis patients

Campanati

Orciani

Lazzarini

et al. 2016

Experimental Dermatology

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“…A phase-contrast microscopy (Leica DM IL; Leica Microsystems GmbH, Wetzlar, Germany) was used to observe the growth and the morphology of cells. For the differentiation potential [14], cells were maintained in Stempro V R osteogenesis, chondrogenesis and adipogenesis differentiation kits (GIBCO, Grand Island, NY, USA). Then, cells were characterized as established in the minimal criteria by Dominici for the definition of human MSCs [13].…”

Section: Isolation Culture and Characterization Of Mscsmentioning

confidence: 99%

“…The amount of mRNA detected in mock and cocultured PsO-MSCs was calculated as X-fold with respect to H-MSCs (expressed as 1) by the 2 2DDCt method [14], where DCt 5 Ct (gene of interest)-Ct (control gene) and D (DCt) 5 DCt (PsO-MSCs alone or co-cultured)-DCt (H-MSCs). X-fold was calculated for the selected genes in all 22 samples of mock MSCs (11 H-MScs and 11 PsO-MSCs) and in the 11 co-cultures (matched randomly).…”

Section: Rt-pcr and Enzyme-linked Immunosorbent Assay (Elisa) Arraymentioning

confidence: 99%

Indirect co-cultures of healthy mesenchymal stem cells restore the physiological phenotypical profile of psoriatic mesenchymal stem cells

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Orciani

Sorgentoni

et al. 2018

Clinical and Experimental Immunology

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Psoriasis microenvironment, characterized by an imbalance between T helper type 1 (Th1)/Th17 and Th2 cytokines and also influences the mesenchymal stem cells (MSCs) phenotypical profile. MSCs from healthy donors (H-MSCs) can exert a strong paracrine effect by secreting active soluble factors, able to modulate the inflammation in the microenvironment. To evaluate the influence of H-MSCs on MSCs from psoriatic patients (PsO-MSCs), H-MSCs and PsO-MSCs were isolated and characterized. Indirect co-culture of H-MSCs with PsO-MSCs was performed; effects on proliferation and expression of cytokines linked to Th1/Th17 and Th2 pathways were assayed before and after co-culture. The results show that before co-culture, proliferation of PsO-MSCs was significantly higher than H-MSCs (P < 0·05) and the levels of secreted cytokines confirmed the imbalance of Th1/Th17 versus the Th2 axis. After co-culture of H-MSCs with PsO-MSCs, healthy MSCs seem to exert a 'positive' influence on PsO-MSCs, driving the inflammatory phenotypical profile of PsO-MSCs towards a physiological pattern. The proliferation rate decreased towards values nearer to those observed in H-MSCs and the secretion of the cytokines that mostly identified the inflammatory microenvironment that characterized psoriasis, such as interleukin (IL)-6, IL-12, IL-13, IL-17A, tumour necrosis factor (TNF)-α and granulocyte-macrophage colony-stimulating factor (G-CSF), is significantly lower in co-cultured PsO-MSCs than in individually cultured PSO-MSCs (P at least < 0·05). In conclusion, our preliminary results seem to provide an intriguing molecular explanation for the ever-increasing evidence of therapeutic efficacy of allogeneic MSCs infusion in psoriatic patients.

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“…Interestingly, both cellular samples failed the adipogenic differentiation; the inability to form adipocytes has already been reported for AF-MSCs (Orciani et al 2011;Lazzarini et al 2014) but it was not still stated for RPESCs. In our previous works, we successfully differentiated MSCs in adipocytes using the same protocol (Orciani et al 2013(Orciani et al , 2015; the molecular analysis by miRNAs profiling (Lazzarini et al, 2014) of AF-MSCs evidenced the fine regulation of adipogenic differentiation by different members of the Smad protein family. The proteins with a pro-adipogenic role were less expressed than proteins related to anti-adipogenic mechanisms.…”

Section: Discussionmentioning

confidence: 98%

Comparative study between amniotic-fluid mesenchymal stem cells and retinal pigmented epithelium (RPE) stem cells ability to differentiate towards RPE cells

et al. 2015

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Dysfunction of the retinal pigmented epithelium (RPE) is one of the first effects of dry age-related macular degeneration (AMD) with consequent blindness. Hence, patients affected by this retinal disorder could benefit from a cell-based transplantation strategy for RPE. Actually, an effective protocol to approach this problem is lacking, though recently, it has been postulated the existence of a subpopulation of RPE stem cells (RPESCs) derived from adult RPE and able to reconstitute a functional RPE. On the other hand, the evidence related to the differentiative potential of human mesenchymal stem cells (MSCs) is continuously increasing. Among others, amniotic fluid-derived MSCs (AF-MSCs) may be a promising candidate, since these cells are characterized by high proliferation and differentiative potential. In this study, AF-MSCs and RPESCs were isolated, characterized to assay their stemness and induced to neuronal/retinal differentiation; specific RPE markers were then analyzed. Our results indicate that RPESCs are more suitable candidates for RPE replacement than AF-MSCs.

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The Response of Breast Cancer Cells to Mesenchymal Stem Cells

Abstract: These data indicate that inflammation caused by breast implants partially affects proliferation of MCF7 but does not influence key mechanisms of tumor development.

Cited by 19 publications

References 30 publications

TNF‐α inhibitors reduce the pathological Th₁–Th₁₇/Th₂ imbalance in cutaneous mesenchymal stem cells of psoriasis patients

TNF‐α inhibitors reduce the pathological Th₁–Th₁₇/Th₂ imbalance in cutaneous mesenchymal stem cells of psoriasis patients

Indirect co-cultures of healthy mesenchymal stem cells restore the physiological phenotypical profile of psoriatic mesenchymal stem cells

Comparative study between amniotic-fluid mesenchymal stem cells and retinal pigmented epithelium (RPE) stem cells ability to differentiate towards RPE cells

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The Response of Breast Cancer Cells to Mesenchymal Stem Cells

Abstract: These data indicate that inflammation caused by breast implants partially affects proliferation of MCF7 but does not influence key mechanisms of tumor development.

Cited by 19 publications

References 30 publications

TNF‐α inhibitors reduce the pathological Th1–Th17/Th2 imbalance in cutaneous mesenchymal stem cells of psoriasis patients

TNF‐α inhibitors reduce the pathological Th1–Th17/Th2 imbalance in cutaneous mesenchymal stem cells of psoriasis patients

Indirect co-cultures of healthy mesenchymal stem cells restore the physiological phenotypical profile of psoriatic mesenchymal stem cells

Comparative study between amniotic-fluid mesenchymal stem cells and retinal pigmented epithelium (RPE) stem cells ability to differentiate towards RPE cells

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TNF‐α inhibitors reduce the pathological Th₁–Th₁₇/Th₂ imbalance in cutaneous mesenchymal stem cells of psoriasis patients

TNF‐α inhibitors reduce the pathological Th₁–Th₁₇/Th₂ imbalance in cutaneous mesenchymal stem cells of psoriasis patients