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 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 ◽  
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 ◽  
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 MicroRNA-210-3p Promotes Chondrogenic Differentiation and Inhibits Adipogenic Differentiation Correlated with HIF-3α Signalling in Bone Marrow Mesenchymal Stem Cells

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Meng Yang ◽  
Xin Yan ◽  
Fu-Zhen Yuan ◽  
Jing Ye ◽  
Ming-Ze Du ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Chondrogenic Differentiation ◽  
Adipogenic Differentiation ◽  
Mrna Translation ◽  
Cartilage Injury ◽  
Self Healing ◽  
Protein Levels ◽  
Marrow Mesenchymal Stem Cells

Cartilage injury of the knee joint is very common. Due to the limited self-healing ability of articular cartilage, osteoarthritis is very likely to occur if left untreated. Bone marrow mesenchymal stem cells (BMMSCs) are widely used in the study of cartilage injury due to their low immunity and good amplification ability, but they still have disadvantages, such as heterogeneous undifferentiated cells. MicroRNAs can regulate the chondrogenic differentiation ability of MSCs by inhibiting or promoting mRNA translation and degradation. In this research, we primarily investigated the effect of microRNA-210-3p (miR-210-3p) on chondrogenic and adipogenic differentiation of BMMSCs in vitro. Our results demonstrate that miR-210-3p promoted chondrogenic differentiation and inhibited adipogenic differentiation of rat BMMSCs, which was related to the HIF-3α signalling pathway. Additionally, miR-210-3p promotes mRNA and protein levels of the chondrogenic expression genes COLII and SOX9 and inhibits mRNA and protein levels of the adipogenic expression genes PPARγ and LPL. Thus, miR-210-3p combined with BMMSCs is a candidate for future clinical applications in cartilage regeneration and could represent a promising new therapeutic target for OA.

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