A Nanofiber Membrane Maintains the Quiescent Phenotype of Hepatic Stellate Cells

Eda, Hiroyuki; Kulig, Katherine M.; Steiner, Toni; Shimada, Hideaki; Patel, Krupali; Park, Eric; Kim, Ernest S.; Borenstein, Jeffrey T.; Neville, Craig M.; Keller, Bradley T.

doi:10.1007/s10620-012-2084-9

Cited by 5 publications

(2 citation statements)

References 45 publications

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“…They play important roles in the regulation of retinoid homeostasis, hepatocyte interactions, and ECM remodeling by producing soluble factors and ECM components as well as matrix metalloproteases (MMP) and their inhibitors. 10,11) However, HSCs can be activated in response to different types of liver injury and differentiate into myofibroblasts. 8,11) Upon activation, HSCs can lead to the deposition of excessive scar matrix into the interstitium as a wound-healing response.…”

mentioning

confidence: 99%

Tenascin-C promotes migration of hepatic stellate cells and production of type I collagen

Huang

Shen

Zheng

et al. 2016

Bioscience, Biotechnology, and Biochemistry

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Tenascin-C (TN-C) is an extracellular matrix glycoprotein markedly upregulated during liver fibrosis. The study is performed to explore the role of TN-C during the growth and activation of hepatic stellate cells (HSCs). We found that TN-C was accumulated accompanying with the HSC activation. Our data on cell migration assay revealed that the rTN-C treatment enhanced HSC migration in a dose- and time-dependent manner, but did not influence their proliferation. HSCs transfected with pTARGET-TN-C overexpression vector displayed increased the type I collagen (Col I) production. TN-C overexpression enhanced the process of HSC activation through TGF-β1 signaling. Moreover, the anti-α9β1 integrin antibody treatment blocked the TN-C-driven Col I increase in rat HSCs. Collectively, TN-C had a positive role in activation of HSCs mediated by TGF-β1 and α9β1 integrin, manifesting elevation of Col I production and promotion of cell migration. Our results provide a potential insight for the therapy of hepatic fibrosis.

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mentioning

confidence: 99%

Tenascin-C promotes migration of hepatic stellate cells and production of type I collagen

Huang

Shen

Zheng

et al. 2016

Bioscience, Biotechnology, and Biochemistry

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“…Thus, the model was unable to support the fully quiescent HSC phenotype. This was probably attributed to the absence of biological cues and its two-dimensional architecture [111]. Mazza in the natural scaffold shows improved viability and proliferation up to day 21 [112].…”

Section: Scaffolds Other Than Hydrogelmentioning

confidence: 99%

Three-dimensional electrospun nanofibrous scaffolds to fabricate in vitro model for liver diseases

Das¹

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Liver extracellular matrix, which has random fibrous network structure, can be closely mimicked by the electrospun fibrous scaffolds. Thus, electrospinning is a promising technology to develop scaffolds for liver tissue engineering. However, the closely packed fibrous mat obtained by the conventional electrospinning process restricts cellular infiltration, thus act like a two-dimensional cell culture model which is different from the in vivo three-dimensional microenvironment. In this study, an interdisciplinary approach was applied to construct a three-dimensional liver tissue mimicking scaffold by using the knowledge of material science and molecular biology. A newly optimized wet electrospinning process was applied to prepare three-dimensional scaffolds with random fibrous network structure. The three-dimensional random electrospun fibers mimic the physical microenvironment, whereas the extracellular matrix proteins grafted on the fiber surface by chemisorption process mimics the chemical microenvironment for the human liver cells. Collagen-I and fibronectin, which are two essential liver extracellular matrix proteins were used to modify the fiber surface. The initial findings suggested that collagen-I modified 3D wet electrospun scaffolds were superior compared to both fibronectin modified scaffold and gold standard sandwich culture in maintaining functions of primary human hepatocytes in vitro. Thus, collagen-I modified 3D electrospun scaffold was used for co-culture of primary human hepatocytes with human hepatic stellate cells to establish the optimum ratio of these two liver cells in the in vitro culture. The ratio was optimized by studying the long-term functional maintenance of primary human hepatocytes. The distinct role of collagen-I and fibronectin for in vitro maintenance of primary human hepatocytes were analyzed and these findings leads to further exploration of the combined effect of these two-essential ECM proteins for the culture of human liver cells in vitro. A series of different ratios of collagen-I to fibronectin were used to chemisorb the electrospun scaffolds. The protein amounts were optimized based on total protein absorbed and the homogeneous distribution of both the proteins on the scaffold surface. Improved protein distribution on the fiber surface was found to enhance functional maintenance of human hepatocytes Abstract ii on 3D electrospun fibrous scaffolds. The findings suggested that cellular microenvironment controls translational and transcriptional properties of the liver cells.The optimized 3D electrospun fibrous scaffolds with optimum ratio of human primary hepatocytes and human hepatic stellate cells were used to fabricate an alcoholic liver disease model. The proposed model was analyzed at different dosage of alcohol under different scaffold conditions. The effect of alcohol was found to be more prominent on the cells cultured on the electrospun fibrous scaffolds modified with both collagen-I and fibronectin when compared to the single protein modified scaffolds, unmodifie...

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Nanostructured Materials in Tissue Engineering

Eyster

Peter

2018

Nano/Micro-Structured Materials for Energy and Biomedical Applications

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A Nanofiber Membrane Maintains the Quiescent Phenotype of Hepatic Stellate Cells

Abstract: HSC cultured on NM retained quiescent characteristics after both short- and long-term culture while activated HSC reverted toward a quiescent state when cultured on NM. Cultures of HSC grown on NM are a useful in vitro model to investigate the mechanisms of activation and deactivation.

Cited by 5 publications

References 45 publications

Tenascin-C promotes migration of hepatic stellate cells and production of type I collagen

Tenascin-C promotes migration of hepatic stellate cells and production of type I collagen

Three-dimensional electrospun nanofibrous scaffolds to fabricate in vitro model for liver diseases

Nanostructured Materials in Tissue Engineering

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