Fibroblast Growth Factor 1-Transfected Adipose-Derived Mesenchymal Stem Cells Promote Angiogenic Proliferation

Hoseini, Seyed Javad; Ghazavi, Hamed; Forouzanfar, Fatemeh; Mashkani, Baratali; Ghorbani, Ahmad; Mahdipour, Elahe; Ghasemi, Faezeh; Sadeghnia, Hamid Reza; Ghayour‐Mobarhan, Majid

doi:10.1089/dna.2016.3546

Cited by 23 publications

(11 citation statements)

References 94 publications

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“…Blunted angiogenic capability was suggested by downregulation of FGF1, PTGIS, and NOSIP. NOSIP expression interferes with endogenous nitric oxide that is critical to cell cycle-related actions such as apoptosis and proliferation (45), while FGF1 promotes angiogenic proliferation (46).…”

Section: Discussionmentioning

confidence: 99%

Alterations in genetic and protein content of swine adipose tissue-derived mesenchymal stem cells in the metabolic syndrome

et al. 2019

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Introduction: Mesenchymal stem cells (MSCs) possess endogenous reparative properties and may serve as an exogenous therapeutic intervention in patients with chronic kidney disease. Cardiovascular risk factors clustering in the metabolic syndrome (MetS) might adversely affect cellular properties. To test the hypothesis that Mets interferes with MSC characteristics, we performed comprehensive comparison of the mRNA, microRNA, and protein content of MSCs isolated from Lean and MetS pigs. Methods: Domestic pigs were fed a 16-week Lean or MetS diet (n=4 each). Expression profiles of co-existing microRNAs, mRNAs, and proteins were obtained by high-throughput sequencing and liquid chromatography-mass spectrometry. TargetScan and ComiR were used to predict target genes of differentially expressed microRNAs, and DAVID 6.7 for functional annotation analysis to rank primary gene ontology categories for the microRNA target genes, mRNAs, and proteins. Results: Differential expression analysis revealed 12 microRNAs upregulated in MetS-MSCs compared to Lean-MSCs (fold change>1.4, p<0.05), which target 7,728 genes, whereas 33 mRNAs and 78 proteins were downregulated (fold change<0.7, p<0.05). Integrated analysis showed that targets of those microRNAs upregulated in MetS-MSCs overlap with at least half of mRNAs and proteins dysregulated in those cells. Functional analysis of overlapping mRNAs and proteins suggest that they are primarily involved in mitochondria, inflammation and transcription. MetS-MSCs also exhibited increased nuclear translocation of nuclear factor kappa-B, associated with increased SA-β-Galactosidase and decreased cytochrome-c oxidase-IV activity. Conclusion: MetS alters the transcriptome and proteome of swine adipose tissue-derived MSCs particularly genes involved in mitochondria, inflammation and transcription regulation. These alterations might limit the reparative function of endogenous MSC and their use as an exogenous regenerative therapy.

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Section: Discussionmentioning

confidence: 99%

Alterations in genetic and protein content of swine adipose tissue-derived mesenchymal stem cells in the metabolic syndrome

et al. 2019

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“…This involves the production of signalling molecules such as TGF-β1, IL-10, CCL9, IFN-α, IFN-β, nitric oxide (NO), VEGF, FGF, HGF, PDGF and membrane-bound vesicles, including microvesicles and exosomes 11 . We therefore hypothesised that these soluble factors, which are present in serum-free MSC-conditioned medium (CM-MSC) 12 – 19 , may be responsible for the therapeutic effects of MSCs 12 – 15 .…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal Stem Cell-Conditioned Medium Reduces Disease Severity and Immune Responses in Inflammatory Arthritis

Kay

Long

Tyler

et al. 2017

Sci Rep

137

116

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We evaluated the therapeutic potential of mesenchymal stem cell-conditioned medium (CM-MSC) as an alternative to cell therapy in an antigen-induced model of arthritis (AIA). Disease severity and cartilage loss were evaluated by histopathological analysis of arthritic knee joints and immunostaining of aggrecan neoepitopes. Cell proliferation was assessed for activated and naïve CD4+ T cells from healthy mice following culture with CM-MSC or co-culture with MSCs. T cell polarization was analysed in CD4+ T cells isolated from spleens and lymph nodes of arthritic mice treated with CM-MSC or MSCs. CM-MSC treatment significantly reduced knee-joint swelling, histopathological signs of AIA, cartilage loss and suppressed TNFα induction. Proliferation of CD4+ cells from spleens of healthy mice was not affected by CM-MSC but reduced when cells were co-cultured with MSCs. In the presence of CM-MSC or MSCs, increases in IL-10 concentration were observed in culture medium. Finally, CD4+ T cells from arthritic mice treated with CM-MSC showed increases in FOXP3 and IL-4 expression and positively affected the Treg:Th17 balance in the tissue. CM-MSC treatment reduces cartilage damage and suppresses immune responses by reducing aggrecan cleavage, enhancing Treg function and adjusting the Treg:Th17 ratio. CM-MSC may provide an effective cell-free therapy for inflammatory arthritis.

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“…FGF1 induced by ERK1/2 signaling could reciprocally regulate proliferation and smooth muscle cell differentiation of ligament-derived EPC-like cells [ 31 ]. In addition, adipose-derived mesenchymal stem cells (AD-MSCs) transfected with FGF1 has been found to promote angiogenic proliferation [ 32 ]. However, the relation of FGF1 with miR-361-5p was hardly discussed.…”

Section: Discussionmentioning

confidence: 99%

Down-regulation of miR-361-5p promotes the viability, migration and tube formation of endothelial progenitor cells via targeting FGF1

et al. 2020

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Transplantion of bone marrow-derived endothelial progenitor cells (EPCs) may be a novel treatment for deep venous thrombosis (DVT). This study probed into the role of miR-361-5p in EPCs and DVT recanalization. EPCs were isolated from male SD rats and identified using flow cytometry. The viability, migration and tube formation of EPCs were examined using MTT assay, wound-healing assay and tube formation assay, respectively. Target gene and potential binding sites between miR-361-5p and FGF1 were predicted by starBase and confirmed by dual-luciferase reporter assay. Relative expressions of miR-361-5p and FGF1 were detected using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot as needed. A DVT model in SD rats was established to investigate the role of EPC with miR-361-5p antagomir in DVT by hematoxylin-eosin staining. EPC was identified as 87.1% positive for CD31, 2.17% positive for CD133, 85.6% positive for vWF and 94.8% positive for VEGFR2. MiR-361-5p antagomir promoted proliferation, migration and tube formation of EPCs and upregulated FGF1 expression, thereby dissolving thrombus in the vein of DVT rats. FGF1 was the target of miR-361-5p, and overexpressed FGF1 reversed the effects of upregulating miR-361-5p on suppressing EPCs. Downregulation of miR-361-5p enhanced thrombus resolution in vivo and promoted EPC viability, migration and angiogenesis in vitro through targeting FGF1. Therefore, miR-361-5p may be a potential therapeutic target for DVT recanalization.

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Fibroblast Growth Factor 1-Transfected Adipose-Derived Mesenchymal Stem Cells Promote Angiogenic Proliferation

Cited by 23 publications

References 94 publications

Alterations in genetic and protein content of swine adipose tissue-derived mesenchymal stem cells in the metabolic syndrome

Alterations in genetic and protein content of swine adipose tissue-derived mesenchymal stem cells in the metabolic syndrome

Mesenchymal Stem Cell-Conditioned Medium Reduces Disease Severity and Immune Responses in Inflammatory Arthritis

Down-regulation of miR-361-5p promotes the viability, migration and tube formation of endothelial progenitor cells via targeting FGF1

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