The differentiation of human MSCs derived from adipose and amniotic tissues into insulin-producing cells, induced by PEI@Fe3O4 nanoparticles-mediated NRSF and SHH silencing

Wang, Rui; Zhang, Dianbao; Zhang, Tao; Zhao, Feng; Lang, Haiyang; Lin, Xuewen; Pang, Xining

doi:10.3892/ijmm.2018.3827

Cited by 5 publications

(5 citation statements)

References 30 publications

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“…It has been reported that hAMSCs possess significant therapeutic effects in multiple disease models, including skin injury, 31 premature ovarian insufficiency, 32 acute liver injury, 33 lung injury, 34 T1 diabetes, 35 chronic kidney disease 36 and so on. MSCs also have shown tremendous potential in anticancer applications because of their innate ability to migrate the tumorigenic sites 37 .…”

Section: Discussionmentioning

confidence: 99%

Human amniotic mesenchymal stem cells inhibit hepatocellular carcinoma in tumour‐bearing mice

Liu

Zhang

et al. 2020

J Cellular Molecular Medi

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Hepatocellular carcinoma (HCC) is the third leading cause of the cancer‐related death in the world. Human amniotic mesenchymal stem cells (hAMSCs) have been characterized with a pluripotency, low immunogenicity and no tumorigenicity. Especially, the immunosuppressive and anti‐inflammatory effects of hAMSCs make them suitable for treating HCC. Here, we reported that hAMSCs administrated by intravenous injection significantly inhibited HCC through suppressing cell proliferation and inducing cell apoptosis in tumour‐bearing mice with Hepg2 cells. Cell tracking experiments with GFP‐labelled hAMSCs showed that the stem cells possessed the ability of migrating to the tumorigenic sites for suppressing tumour growth. Importantly, both hAMSCs and the conditional media (hAMSC‐CM) have the similar antitumour effects in vitro, suggesting that hAMSCs‐derived cytokines might be involved in their antitumour effects. Antibody array assay showed that hAMSCs highly expressed dickkopf‐3 (DKK‐3), dickkopf‐1 (DKK‐1) and insulin‐like growth factor‐binding protein 3 (IGFBP‐3). Furthermore, the antitumour effects of hAMSCs were further confirmed by applications of the antibodies or the specific siRNAs of DKK‐3, DKK‐1 and IGFBP‐3 in vitro. Mechanically, hAMSCs‐derived DKK‐3, DKK‐1 and IGFBP‐3 markedly inhibited cell proliferation and promoted apoptosis of Hepg2 cells through suppressing the Wnt/β‐catenin signalling pathway and IGF‐1R‐mediated PI3K/AKT signalling pathway, respectively. Taken together, our study demonstrated that hAMSCs possess significant antitumour effects in vivo and in vitro and might provide a novel strategy for HCC treatment clinically.

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Section: Discussionmentioning

confidence: 99%

Human amniotic mesenchymal stem cells inhibit hepatocellular carcinoma in tumour‐bearing mice

Liu

Zhang

et al. 2020

J Cellular Molecular Medi

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“…49,50 After comparing the expression of endogenous Cdc42 protein in ADSCs and rat islets, in accordance with previous studies, we successfully induce ADSCs into IPCs. [51][52][53] Our data indicate that high glucose (4.5 g/L D-glucose) and DMSO (10%) significantly promote the induction of IPCs from ADSCs. Interestingly, after we constructed DTZ staining to further verify the induction of IPCs, some cells in the control group fell off, but the induction group remained.…”

Section: Discussionmentioning

confidence: 99%

<p>Cdc42 Promotes ADSC-Derived IPC Induction, Proliferation, And Insulin Secretion Via Wnt/β-Catenin Signaling</p>

Xiao

Huang

Qian

et al. 2019

DMSO

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Type 1 diabetes mellitus (T1DM) is characterized by irreversible islet β cell destruction. Accumulative evidence indicated that Cdc42 and Wnt/β-catenin signaling both play a critical role in the pathogenesis and development of T1DM. Further, bio-molecular mechanisms in adipose-derived mesenchymal stem cells (ADSCs)-derived insulin-producing cells (IPCs) remain largely unknown. Our aim was to investigate the underlying mechanism of Cdc42/Wnt/β-catenin pathway in ADSC-derived IPCs, which may provide new insights into the therapeutic strategy for T1DM patients. Methods: ADSC induction was accomplished with DMSO under high-glucose condition. ML141 (Cdc42 inhibitor) and Wnt-3a (Wnt signaling activator) were administered to ADSCs from day 2 until the induction finished. Morphological changes were determined by an inverted microscope. Dithizone staining was employed to evaluate the induction of ADSCderived IPCs. qPCR and Western blotting were employed to measure the mRNA and protein expression level of islet cell development-related genes and Wnt signaling-related genes. The proliferation ability of ADSC-derived IPCs was also detected with a cell counting kit (CCK) assay. The expression and secretion of Insulin were detected with immunofluorescence test and enzyme-linked immunosorbent assay (ELISA) respectively. Results: During induction, morphological characters of ADSCs changed into spindle and round shape, and formed islet-line cell clusters, with brown dithizone-stained cytoplasm. Expression levels of islet cell development-related genes were up-regulated in ADSCderived IPCs. Wnt-3a promoted Wnt signaling markers and islet cell development-related gene expression at mRNA and protein levels, while ML141 played a negative effect. Wnt-3a promoted ADSC-derived IPC proliferation and glucose-stimulated insulin secretion (GSIS), while ML141 played a negative effect. Conclusion: Our research demonstrated that DMSO and high-glucose condition can induce ADSCs into IPCs, and Wnt signaling promotes the induction. Cdc42 may promote IPC induction, IPC proliferation and insulin secretion via Wnt/β-catenin pathway, meaning that Cdc42 may be regarded as a potential target in the treatment of T1DM.

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“…The reported advantages of hAMSCs include higher cell harvest at the beginning, low donor site morbidity, more "youthful" phenotype, compatibility for use in allogeneic transplants, and powerful immunomodulatory properties compared with hBMSCs and hADSCs (20)(21)(22). Research has proven that hAMSCs protect multiple disease models, including chronic kidney disease (23), T1 diabetes (24), and smoke-induced lung injury (25). However, no study has yet revealed the function of hAMSCs in APAP-induced liver injury.…”

Section: Discussionmentioning

confidence: 99%

Human amniotic mesenchymal stromal cells alleviate acute liver injury by inhibiting the pro-inflammatory response of liver resident macrophage through autophagy

et al. 2019

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Background: The activation and polarization of macrophages are crucial during the pathogenesis of liver injury induced by the toxin. Human amniotic mesenchymal stromal cells (hAMSCs) are newly identified mesenchymal stem cells and have been shown to have an immunoregulatory ability for multiple autoimmune diseases. Methods: Mice were intraperitoneally injected with Acetaminophen (APAP) to establish a liver injury model. hAMSCs were injected through the tail vein, and the liver function was observed through a liver function and pathology analysis. To test the regulative ability of hAMSCs in vitro, the supernatant of hAMSCs were collected and co-cultured with Kupffer cells (KCs). Liposome was used to abolish the function of KCs in vivo. Results: Infusion of hAMSCs reduced the level of liver function injury and inflammation expression in APAP-induced liver injury. hAMSCs markedly promoted M2 polarization of KCs instead of M1 polarization in vitro. Furthermore, the mechanism study also proved that hAMSCs reduced autophagy, as revealed by down-regulated LC3B-II levels. The elimination of KCs in vivo abolished the protective ability of hAMSCs in liver injury, which resulted in a significant increase of liver pathogenesis along with an increase in alanine aminotransaminase (ALT) and aspartate aminotransaminase (AST) levels. Conclusions: Our results proved that hAMSCs suppressed M1 polarization and promoted M2 polarization of KCs through regulating autophagy in the model of APAP-treated livers. Thus, the injury of the liver was attenuated. This study provides us a new therapeutic strategy for the disease of acute liver injury.

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The differentiation of human MSCs derived from adipose and amniotic tissues into insulin-producing cells, induced by PEI@Fe3O4 nanoparticles-mediated NRSF and SHH silencing

Cited by 5 publications

References 30 publications

Human amniotic mesenchymal stem cells inhibit hepatocellular carcinoma in tumour‐bearing mice

Human amniotic mesenchymal stem cells inhibit hepatocellular carcinoma in tumour‐bearing mice

<p>Cdc42 Promotes ADSC-Derived IPC Induction, Proliferation, And Insulin Secretion Via Wnt/β-Catenin Signaling</p>

Human amniotic mesenchymal stromal cells alleviate acute liver injury by inhibiting the pro-inflammatory response of liver resident macrophage through autophagy

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