Inhibiting glycogen synthase kinase-3 and transforming growth factor-β signaling to promote epithelial transition of human adipose mesenchymal stem cells

Setiawan, Melina; Tan, Xiao-wei; Goh, Tze-Wei; Yam, Gary Hin‐Fai; Mehta, Jodhbir S.

doi:10.1016/j.bbrc.2017.07.036

Cited by 21 publications

(19 citation statements)

References 37 publications

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“…and upregulated epithelial genes (E-cadherin, P63, etc.) [54]. In line with the degree of hASC differentiation, the mRNA expression levels of E-cadherin in differentiated cells were higher than those with low or no significant differentiation (Fig.…”

Section: Gene Expression Analysissupporting

confidence: 58%

“…MET involves the progressive increase of epithelial cell polarity and upregulation of junctional complexes to form tight junctions at the apex of the lateral domain and the organization of cytoskeletal structures and organelles [53], accompanied by downregulated mesenchymal genes (E-cadherin, ZEB1, etc.) and upregulated epithelial genes (E-cadherin, P63, et c) [54]. In the current research, MET was hypothesized to preliminarily explain the differentiation of hASCs in 3D system at ALI towards keratinocytes.…”

Section: Discussionmentioning

confidence: 85%

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Epithelial differentiation of human adipose-derived stem cells (hASCs) undergoing three-dimensional (3D) cultivation with collagen sponge scaffold (CSS) via an indirect co-culture strategy

Gao

et al. 2020

Stem Cell Res Ther

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Background: Three-dimensional (3D) cultivation with biomaterials was proposed to facilitate stem cell epithelial differentiation for wound healing. However, whether human adipose-derived stem cells (hASCs) on collagen sponge scaffold (CSS) better differentiate to keratinocytes remains unclear. Methods: 3D cultivation with CSS on hASC epidermal differentiation co-cultured with HaCaT cells at air-liquid interface (ALI) was compared with two-dimensional (2D) form and cultivation without "co-culture" or "ALI." Cellular morphology, cell adhesion, and growth condition were evaluated, followed by the protein and gene expression of keratin 14 (K14, keratinocyte specific marker). Results: Typical cobblestone morphology of keratinocytes was remarkably observed in co-cultured hASCs at ALI, but those seeded on the CSS exhibited more keratinocyte-like cells under an invert microscope and scanning electron microscope. Desired cell adhesion and proliferation were confirmed in 3D differentiation groups by rhodamine-labeled phalloidin staining, consistent with H&E staining. Compared with those cultured in 2D culture system or without "ALI," immunofluorescence staining and gene expression analysis revealed hASCs co-cultured over CSS expressed K14 at higher levels at day 15. Conclusions: CSS is positive to promote epithelial differentiation of hASCs, which will foster a deeper understanding of artificial dermis in skin wound healing and regeneration.

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Section: Gene Expression Analysissupporting

confidence: 58%

Section: Discussionmentioning

confidence: 85%

Epithelial differentiation of human adipose-derived stem cells (hASCs) undergoing three-dimensional (3D) cultivation with collagen sponge scaffold (CSS) via an indirect co-culture strategy

Gao

et al. 2020

Stem Cell Res Ther

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“…As for the cell cycle, interestingly we noticed that it is undisturbed. Recently, significant gene ontology terms enriched in the upregulated gene sets representing cell cycle were detected in human adipose MSC (Setiawan, Tan, Goh, Hin-Fai Yam, & Mehta, 2017). However, there's no detailed information available for the impact of Repsox on the cell cycle.…”

Section: Discussionmentioning

confidence: 99%

Inhibiting transforming growth factor‐β signaling regulates in vitro maintenance and differentiation of bovine bone marrow mesenchymal stem cells

Zhao

Zhu

et al. 2018

J Exp Zool Pt B

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Bovine bone marrow mesenchymal stem cells (bBMSC) are potential stem cell source which can be used for multipurpose. However, their application is limited because the in vitro maintenance of these cells is usually accompanied by aging and multipotency losing. Considering transforming growth factor‐β (TGF‐β) pathway inhibitor Repsox is beneficial for cell reprogramming, here we investigated its impacts on the maintenance and differentiation of bBMSC. The bBMSC were enriched and characterized by morphology, immunofluorescent staining, flow cytometry, and multilineage differentiation. The impacts of Repsox on their proliferation, apoptosis, cell cycle, multipotency, and differentiation were examined by Cell Counting Kit‐8 (CCK‐8), real‐time polymerase chain reaction, induced differentiation and specific staining. The results showed that highly purified cluster of diffrentiation 73+ (CD73 +)/CD90 +/CD105 +/CD34 −/CD45 − bBMSC with adipogenic, osteogenic, and chondrogenic differentiation capacities were enriched. Repsox treatments (5 μM, 48 hr) enhanced the messenger RNA mRNA levels of the proliferation gene (telomerase reverse transcriptase [ TERT]; basic fibroblast growth factor [ bFGF]), apoptosis‐related gene ( bax and Bcl2), antiapoptosis ratio ( Bcl2/bax), and pluripotency marker gene ( Oct4, Sox2, and Nanog), instead of changing the cell cycle, in bBMSC. Repsox treatments also enhanced the osteogenic differentiation but attenuated the chondrogenic differentiation of bBMSC, concomitant with decreased Smad2 and increased Smad3/4 expressions in TGF‐β pathway. Collectively, inhibiting TGF‐β/Smad signaling by Repsox regulates the in vitro maintenance and differentiation of bBMSC.

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“…Studies of epithelial differentiation of human adipose mesenchymal stem cells by inhibiting glycogen synthase kinase 3 (GSK-3) and transforming growth factor beta (TGFb) showed positive results. In the study of ADSCs, at the second passage, cells were treated with CHIR99021 (GSK-3 inhibitor), E-616452 (TGFb1 kinase inhibitor), A-83-01 (TGFb1 receptor inhibitor), and VA (histone deacetylase inhibitor) (Setiawan et al 2017). It is also shown that induction of the MSC differentiation into hepatocytes is possible using only GSK3 inhibitor (Huang et al 2017).…”

Section: Valproic Acid Effect On Tumor Cellsmentioning

confidence: 99%

Pharmacological modulation of cell functional activity with valproic acid and erythropoietin

Golubinskaya¹,

Sarycheva²,

Burda³

et al. 2019

RRP

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Introduction: Valproic acid (VA) is carboxylic acid with a branched chain, which is used as an antiepileptic drug. Valproic acid influence on cells in vivo: VA, which is an antiepileptic drug, is also a teratogen, which causes defects of a neural tube and an axial skeleton, although the mechanisms are not yet fully clear. Valproic acid influence on mesenchymal stem cells (MSC) in vitro: It is shown that valproic acid reduces the intracellular level of oxygen active forms. Valproic acid effect on tumor cells: VA inhibits tumor growth through several mechanisms, including the cell cycle stop, differentiation induction and inhibition of growth of tumor vessels. Valproic acid influence on enzymes: It affects mainly GSK-3. Valproic acid influence on animals’ cells: It is shown that VA can significantly improve an ability to develop in vitro and improve nuclear reprogramming of embryos. Erythropoietin (EPO): Is an hypoxia-induced hormone and a cytokine, which is necessary for normal erythropoiesis. EPO is widely used in in vitro experiments. Conclusion: Thus, the influence of VA and EPO on cells can be used in cell technologies.

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Inhibiting glycogen synthase kinase-3 and transforming growth factor-β signaling to promote epithelial transition of human adipose mesenchymal stem cells

Cited by 21 publications

References 37 publications

Epithelial differentiation of human adipose-derived stem cells (hASCs) undergoing three-dimensional (3D) cultivation with collagen sponge scaffold (CSS) via an indirect co-culture strategy

Epithelial differentiation of human adipose-derived stem cells (hASCs) undergoing three-dimensional (3D) cultivation with collagen sponge scaffold (CSS) via an indirect co-culture strategy

Inhibiting transforming growth factor‐β signaling regulates in vitro maintenance and differentiation of bovine bone marrow mesenchymal stem cells

Pharmacological modulation of cell functional activity with valproic acid and erythropoietin

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