scholarly journals Functionally enhanced placenta-derived mesenchymal stem cells inhibit adipogenesis in orbital fibroblasts with Graves’ ophthalmopathy

2020 ◽  
Author(s):  
Jae Yeon Kim ◽  
Sohae Park ◽  
Hyun-Jung Lee ◽  
Helen Lew ◽  
Gi Jin Kim
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Protein Expression ◽  
Molecular Mechanisms ◽  
Adipogenic Differentiation ◽  
Graves Ophthalmopathy ◽  
Mrna And Protein Expression ◽  
Tissue Specimens ◽  
Phosphatase Of Regenerating Liver

Abstract Background: Placenta-derived mesenchymal stem cells (PD-MSCs) have unique immunomodulatory properties, and phosphatase of regenerating liver-1 (PRL-1) regulates the self-renewal ability of stem cells and promotes proliferation. Graves’ ophthalmopathy (GO) is an autoimmune inflammatory disease of the orbit and is characterized by increased orbital levels of adipose tissue. Because the mechanism of inhibiting adipogenesis in orbital fibroblast (OF) with GO patients remains uncertain, the major objective of the present study is to investigate the mechanisms by which PRL-1-overexpressing PD-MSCs (PD-MSCsPRL-1, PRL-1+) alleviate adipogenesis in OFs derived from GO patients.Methods: Primary OFs were isolated from orbital adipose tissue specimens from GO patients. After maturation as adipogenic differentiation, normal and GO-derived OFs were cocultured with naïve PD-MSCs and PD-MSCsPRL-1. Western blotting was conducted to evaluate the molecular mechanisms associated with adipogenesis inhibition in GO.Results: The characteristics of PD-MSCsPRL-1 were similar to those of naïve cells. OFs from GO patients underwent stimulated adipocyte differentiation and had significantly decreased lipid accumulation after coculture with PD-MSCsPRL-1 compared with naïve cell coculture. The mRNA and protein expression of adipogenic markers was decreased in PD-MSCsPRL-1. The protein expression of phosphorylated PI3K/AKT/mTOR in OFs from GO patients was downregulated by coculture with PD-MSCsPRL-1, which secreted IGFBPs. Interestingly, IGFBP2, -4, and -7 expression in PD-MSCsPRL-1, which was mediated by integrin alpha 4 (ITGA4) and integrin beta 7 (ITGB7), was higher than that in naïve cells and upregulated phosphorylated focal adhesion kinase (pFAK) downstream factors.Conclusion: In summary, PD-MSCPRL-1-secreted IGFBPs inhibit adipogenesis in OFs from GO patients by upregulating FAK and blocking IGF, providing a novel therapeutic strategy using functionally enhanced MSCs to treat degenerative diseases.

scholarly journals Functionally enhanced placenta-derived mesenchymal stem cells inhibit adipogenesis in orbital fibroblast with graves’ ophthalmopathy

2020 ◽  
Author(s):  
Jae Yeon Kim ◽  
Sohae Park ◽  
Hyun-Jung Lee ◽  
Helen Lew ◽  
Gi Jin Kim
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Molecular Mechanisms ◽  
Adipogenic Differentiation ◽  
Graves Ophthalmopathy ◽  
Mrna And Protein Expression ◽  
Orbital Fibroblast ◽  
Tissue Specimens ◽  
Phosphatase Of Regenerating Liver

Abstract Background: Placenta-derived mesenchymal stem cells (PD-MSCs) have unique immunomodulatory properties, and Phosphatase of regenerating liver-1 (PRL-1) regulates self-renewal ability of stem cells and promotes proliferation. Graves’ ophthalmopathy (GO) is an autoimmune inflammatory disease of the orbit and is characterized by increased orbital contents involving adipose tissue. Because the mechanism of inhibiting adipogenesis in orbital fibroblast (OF) with GO patients remains uncertain, the major objective is to investigate mechanisms alleviating adipogenesis by PRL-1 overexpressing PD-MSCs (PD-MSCsPRL-1, PRL-1+) in OF derived from GO patients. Methods: primary OFs from patients with GO were isolated from orbital adipose tissue specimens. After maturation as adipogenic differentiation, normal and GO-derived OF were cocultured with naïve and PD-MSCsPRL-1. Western blotting were conducted for evaluating molecular mechanisms for inhibiting adipogenesis in GO. Results: The characterizations of PD-MSCsPRL-1 were similar to naïve. OF with GO patients stimulated adipocyte differentiation were significantly decreased lipid accumulation by cocultivation with PD-MSCsPRL-1 comparing with naïve. The mRNA and protein expression of adipogenic markers was declined in PD-MSCsPRL-1. The expression of pPI3K/AKT/mTOR protein in OF with GO patients was downregulated by cocultivation with PD-MSCsPRL-1 secreted IGFBPs. Interestingly, IGFBP2, 4, and 7 expressions through integrin alpha 4 (ITGA4) and beta 7 (ITGB7) in PD-MSCsPRL-1 were higher than naïve and upregulated pFAK downstream factor. Conclusion: Taken together, secreted IGFBPs by PD-MSCsPRL-1 via upregulating FAK and blocking IGF inhibit adipogenesis of OF with GO patients, providing novel therapeutic approach using functionally enhanced MSCs potential for degenerative diseases.

scholarly journals Functionally enhanced placenta-derived mesenchymal stem cells inhibit adipogenesis in orbital fibroblasts with Graves’ ophthalmopathy

2020 ◽  
Author(s):  
Jae Yeon Kim ◽  
Sohae Park ◽  
Hyun-Jung Lee ◽  
Helen Lew ◽  
Gi Jin Kim
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Adipogenic Differentiation ◽  
Protein Levels ◽  
Graves Ophthalmopathy ◽  
Therapeutic Mechanism ◽  
Mrna And Protein Expression ◽  
Tissue Specimens ◽  
Phosphatase Of Regenerating Liver

Abstract Background: Placenta-derived mesenchymal stem cells (PD-MSCs) have unique immunomodulatory properties. Phosphatase of regenerating liver-1 (PRL-1) regulates the self-renewal ability of stem cells and promotes proliferation. Graves’ ophthalmopathy (GO) is an autoimmune inflammatory disease of the orbit and is characterized by increased orbital levels of adipose tissue. Here, we evaluated the therapeutic mechanism for regulation of adipogenesis by PRL-1-overexpressing PD-MSCs (PD-MSCsPRL-1, PRL-1+) in orbital fibroblast (OF) with GO patients.Methods: Primary OFs were isolated from orbital adipose tissue specimens from GO patients. After maturation as adipogenic differentiation, normal and GO-derived OFs were cocultured with naïve and PD-MSCsPRL-1. We analyzed the protein levels of adipogenesis markers and their signaling pathways in OF from GO patients. Results: The characteristics of PD-MSCsPRL-1 were similar to those of naïve cells. OFs from GO patients induced adipocyte differentiation and had significantly decreased a lipid accumulation after coculture with PD-MSCsPRL-1 compared to naïve. The mRNA and protein expression of adipogenic markers was decreased in PD-MSCsPRL-1. Insulin-like growth factor-binding proteins (IGFBPs) secreting PD-MSCsPRL-1 downregulated the phosphorylated PI3K/AKT/mTOR expression in OFs from GO patients. Interestingly, IGFBP2, -4, and -7 expression in PD-MSCsPRL-1, which was mediated by integrin alpha 4 (ITGA4) and beta 7 (ITGB7), was higher than that in naïve cells and upregulated phosphorylated FAK downstream factors.Conclusion: In summary, IGFBPs secreting PD-MSCPRL-1 inhibit adipogenesis in OFs from GO patients by upregulating phosphorylated FAK, providing a novel therapeutic strategy using functionally enhanced MSCs to treat degenerative diseases.

scholarly journals Functionally enhanced placenta-derived mesenchymal stem cells inhibit adipogenesis in orbital fibroblasts with Graves’ ophthalmopathy

2020 ◽  
Author(s):  
Jae Yeon Kim ◽  
Sohae Park ◽  
Hyun-Jung Lee ◽  
Helen Lew ◽  
Gi Jin Kim
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Adipogenic Differentiation ◽  
Protein Levels ◽  
Graves Ophthalmopathy ◽  
Transfection Method ◽  
Mrna And Protein Expression ◽  
Tissue Specimens ◽  
Phosphatase Of Regenerating Liver

Abstract Background: Placenta-derived mesenchymal stem cells (PD-MSCs) have unique immunomodulatory properties. Phosphatase of regenerating liver-1 (PRL-1) regulates the self-renewal ability of stem cells and promotes proliferation. Graves’ ophthalmopathy (GO) is an autoimmune inflammatory disease of the orbit and is characterized by increased orbital levels of adipose tissue. Here, we evaluated the therapeutic mechanism for regulation of adipogenesis by PRL-1-overexpressing PD-MSCs (PD-MSCsPRL-1, PRL-1+) in orbital fibroblast (OF) with GO patients.Methods: PD-MSCs isolated from human placenta were transfected with the PRL-1 gene using nonviral transfection method. Primary OFs were isolated from orbital adipose tissue specimens from GO patients. After maturation as adipogenic differentiation, normal and GO-derived OFs were cocultured with naïve and PD-MSCsPRL-1. We analyzed the protein levels of adipogenesis markers and their signaling pathways in OF from GO patients. Results: The characteristics of PD-MSCsPRL-1 were similar to those of naïve cells. OFs from GO patients induced adipocyte differentiation and had significantly decreased a lipid accumulation after coculture with PD-MSCsPRL-1 compared to naïve cells. The mRNA and protein expression of adipogenic markers was decreased in PD-MSCsPRL-1. Insulin-like growth factor-binding proteins (IGFBPs) secreting PD-MSCsPRL-1 downregulated the phosphorylated PI3K/AKT/mTOR expression in OFs from GO patients. Interestingly, IGFBP2, -4, -6, and -7 expression in PD-MSCsPRL-1, which was mediated by integrin alpha 4 (ITGA4) and beta 7 (ITGB7), was higher than that in naïve cells and upregulated phosphorylated FAK downstream factor.Conclusion: In summary, IGFBPs secreting PD-MSCPRL-1 inhibit adipogenesis in OFs from GO patients by upregulating phosphorylated FAK and downregulating PI3K/AKT/mTOR signaling pathway. The functional enhancement of PD-MSCs by nonviral gene modification provides a novel therapeutic strategy for the treatment of degenerative diseases.

scholarly journals Functionally enhanced placenta-derived mesenchymal stem cells inhibit adipogenesis in orbital fibroblasts with Graves’ ophthalmopathy

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Jae Yeon Kim ◽  
Sohae Park ◽  
Hyun-Jung Lee ◽  
Helen Lew ◽  
Gi Jin Kim
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Adipogenic Differentiation ◽  
Protein Levels ◽  
Graves Ophthalmopathy ◽  
Transfection Method ◽  
Mrna And Protein Expression ◽  
Tissue Specimens ◽  
Phosphatase Of Regenerating Liver

Abstract Background Placenta-derived mesenchymal stem cells (PD-MSCs) have unique immunomodulatory properties. Phosphatase of regenerating liver-1 (PRL-1) regulates the self-renewal ability of stem cells and promotes proliferation. Graves’ ophthalmopathy (GO) is an autoimmune inflammatory disease of the orbit and is characterized by increased orbital levels of adipose tissue. Here, we evaluated the therapeutic mechanism for regulation of adipogenesis by PRL-1-overexpressing PD-MSCs (PD-MSCsPRL-1, PRL-1+) in orbital fibroblast (OF) with GO patients. Methods PD-MSCs isolated from human placenta were transfected with the PRL-1 gene using nonviral transfection method. Primary OFs were isolated from orbital adipose tissue specimens from GO patients. After maturation as adipogenic differentiation, normal and GO-derived OFs were cocultured with naïve and PD-MSCsPRL-1. We analyzed the protein levels of adipogenesis markers and their signaling pathways in OFs from GO patients. Results The characteristics of PD-MSCsPRL-1 were similar to those of naïve cells. OFs from GO patients induced adipocyte differentiation and had significantly decreased a lipid accumulation after coculture with PD-MSCsPRL-1 compared to naïve cells. The mRNA and protein expression of adipogenic markers was decreased in PD-MSCsPRL-1. Insulin-like growth factor-binding proteins (IGFBPs) secreting PD-MSCsPRL-1 downregulated the phosphorylated PI3K/AKT/mTOR expression in OFs from GO patients. Interestingly, IGFBP2, − 4, − 6, and − 7 expression in PD-MSCsPRL-1, which was mediated by integrin alpha 4 (ITGA4) and beta 7 (ITGB7), was higher than that in naïve cells and upregulated phosphorylated FAK downstream factor. Conclusion In summary, IGFBPs secreting PD-MSCPRL-1 inhibit adipogenesis in OFs from GO patients by upregulating phosphorylated FAK and downregulating PI3K/AKT/mTOR signaling pathway. The functional enhancement of PD-MSCs by nonviral gene modification provides a novel therapeutic strategy for the treatment of degenerative diseases.

scholarly journals Regulation of CXCR6 Expression on Adipocytes and Osteoblasts Differentiated from Human Adipose Tissue-Derived Mesenchymal Stem Cells

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Seung-Cheol Lee ◽  
Yoo-Jung Lee ◽  
Min Kyoung Shin ◽  
Jung-Suk Sung
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Cell Activation ◽  
Molecular Mechanisms ◽  
De Novo ◽  
Human Mesenchymal Stem Cells ◽  
De Novo Synthesis ◽  
Differentiation Potential ◽  
Differentiated Cells

Human mesenchymal stem cells derived from adipose tissue (hADMSCs) are a desirable candidate in regenerative medicine. hADMSCs secrete growth factors, cytokines, and chemokines and also express various receptors that are important in cell activation, differentiation, and migration to injured tissue. We showed that the expression level of chemokine receptor CXCR6 was significantly increased by ~2.5-fold in adipogenic-differentiated cells (Ad), but not in osteogenic-differentiated cells (Os) when compared with hADMSCs. However, regulation of CXCR6 expression on hADMSCs by using lentiviral particles did not affect the differentiation potential of hADMSCs. Increased expression of CXCR6 on Ad was mediated by both receptor recycling, which was in turn regulated by secretion of CXCL16, and de novo synthesis. The level of soluble CXCL16 was highly increased in both Ad and Os in particular, which inversely correlates with the expression on a transmembrane-bound form of CXCL16 that is cleaved by disintegrin and metalloproteinase. We concluded that the expression of CXCR6 is regulated by receptor degradation or recycling when it is internalized by interaction with CXCL16 and by de novo synthesis of CXCR6. Overall, our study may provide an insight into the molecular mechanisms of the CXCR6 reciprocally expressed on differentiated cells from hADMSCs.

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