Reconstruction of hepatic stellate cell-incorporated liver capillary structures in small hepatocyte tri-culture using microporous membranes

Kasuya, Junichi; Sudo, Ryo; Masuda, Genta; Mitaka, Toshihiro; Ikeda, Mariko; Tanishita, Kazuo

doi:10.1002/term.1630

Cited by 9 publications

(9 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Multicellular coculture models [, , ] are gaining momentum for various applications. A recent study described the use of human umbilical vein endothelial cells to stabilize hepatoblastoma C3A cells and modulate drug‐induced hepatotoxicity [].…”

Section: Discussionmentioning

confidence: 99%

“…Endothelial cells from hPSCs were used to vascularize liver constructs []. These are part of the advances to model liver vasculatures, using multiple stromal cell types alongside hepatocytes to develop liver lobule and sinusoid‐like structures [, , ], for hepatotoxicity screening and tissue‐engineering applications. We are the first to report a human stem cell‐derived endothelial‐hepatic platform for efficacy testing of complex compounds.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Human Stem Cell-Derived Endothelial-Hepatic Platform for Efficacy Testing of Vascular-Protective Metabolites from Nutraceuticals

Narmada

Goh

et al. 2016

Stem Cells Translational Medicine

View full text Add to dashboard Cite

Atherosclerosis underlies many cardiovascular and cerebrovascular diseases. Nutraceuticals are emerging as a therapeutic moiety for restoring vascular health. Unlike small‐molecule drugs, the complexity of ingredients in nutraceuticals often confounds evaluation of their efficacy in preclinical evaluation. It is recognized that the liver is a vital organ in processing complex compounds into bioactive metabolites. In this work, we developed a coculture system of human pluripotent stem cell‐derived endothelial cells (hPSC‐ECs) and human pluripotent stem cell‐derived hepatocytes (hPSC‐HEPs) for predicting vascular‐protective effects of nutraceuticals. To validate our model, two compounds (quercetin and genistein), known to have anti‐inflammatory effects on vasculatures, were selected. We found that both quercetin and genistein were ineffective at suppressing inflammatory activation by interleukin‐1β owing to limited metabolic activity of hPSC‐ECs. Conversely, hPSC‐HEPs demonstrated metabolic capacity to break down both nutraceuticals into primary and secondary metabolites. When hPSC‐HEPs were cocultured with hPSC‐ECs to permit paracrine interactions, the continuous turnover of metabolites mitigated interleukin‐1β stimulation on hPSC‐ECs. We observed significant reductions in inflammatory gene expressions, nuclear translocation of nuclear factor κB, and interleukin‐8 production. Thus, integration of hPSC‐HEPs could accurately reproduce systemic effects involved in drug metabolism in vivo to unravel beneficial constituents in nutraceuticals. This physiologically relevant endothelial‐hepatic platform would be a great resource in predicting the efficacy of complex nutraceuticals and mechanistic interrogation of vascular‐targeting candidate compounds. Stem Cells Translational Medicine 2017;6:851–863

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Human Stem Cell-Derived Endothelial-Hepatic Platform for Efficacy Testing of Vascular-Protective Metabolites from Nutraceuticals

Narmada

Goh

et al. 2016

Stem Cells Translational Medicine

View full text Add to dashboard Cite

show abstract

“…Finally, we demonstrated reconstruction of HSC-incorporated sinusoidal structures 47 . In the sinusoids, HSCs surrounded the outer surface of EC capillary structures.…”

Section: Functional Liver Tissue Engineering With Microporous Membranesmentioning

confidence: 94%

Microporous membrane-based liver tissue engineering for the reconstruction of three-dimensional functional liver tissues in vitro

Kasuya

Tanishita

2012

Biomatter

Self Cite

View full text Add to dashboard Cite

To meet the increasing demand for liver tissue engineering, various three-dimensional (3D) liver cell culture techniques have been developed. Nevertheless, conventional liver cell culture techniques involving the suspending cells in extracellular matrix (ECM) components and the seeding of cells into 3D biodegradable scaffolds have an intrinsic shortcoming, low cell-scaffold ratios. We have developed a microporous membrane-based liver cell culture technique. Cell behaviors and tissue organization can be controlled by membrane geometry, and cell-dense thick tissues can be reconstructed by layering cells cultured on biodegradable microporous membranes. Applications extend from liver parenchymal cell monoculture to multi-cell type cultures for the reconstruction of 3D functional liver tissue. This review focuses on the expanding role for microporous membranes in liver tissue engineering, primarily from our research.

show abstract

“…This process was mediated, in part, by platelet-derived growth factor (PDGF) signaling. In addition, these HSCs firmly lined the outer surface of the EC capillary-like structures with long cytoplasmic processes (Kasuya et al 2015) (Fig. 16.14).…”

Section: Coculture Of Ecs and Hepatocytes In A Microfluidic Device: Amentioning

confidence: 98%

Integrated Vascular Engineering: Vascularization of Reconstructed Tissue

Sudo

Chung²,

Shin

et al. 2016

Vascular Engineering

Self Cite

View full text Add to dashboard Cite

In this chapter, we describe culture methods to construct microvascular networks as well as approaches to integrating capillary networks with 3D epithelial tissueengineered constructs. First, culture models of microvascular networks such as in vitro angiogenesis and vasculogenesis models are introduced. Using these culture models, the roles of endothelial cells (ECs), such as endothelial tip, stalk, and phalanx cells, are demonstrated. Additionally, regulatory factors, including both biochemical and biophysical factors, are discussed in the context of 3D capillary formation, including the process of vascular development, growth, and maturation. Next, we focus on the use of microfluidics technologies for investigating capillary morphogenesis. Examples of 3D capillary formation assays with growth factor gradients and different extracellular matrix materials are described. Cocultures of ECs and the other cell types in microfluidic devices are also introduced to show the potential of microfluidic vascular formation models. The vascularization of constructed tissues is discussed from the viewpoints of horizontal and vertical approaches for combining capillary structures and epithelial tissues in vitro. Finally, the concept of integrated vascular engineering and future perspectives are discussed. General Introduction for In Vitro Capillary FormationBlood vessels are tubular structures through which blood passes to provide oxygen and nutrients to individual cells within tissues and organs. Because oxygen and nutrients are the most important fundamental factors for vital activity, blood vessels are essential tissues in the body. The luminal surface of blood vessels is covered by endothelial cells (ECs). Thus, we need to understand how ECs form blood vessels for the development of vascular tissue engineering. In particular, in the context of tissue engineering for three-dimensional (3D) tissues and organs, construction of microvascular networks, rather than large blood vessels, has a high priority.There are two processes of microvessel formation in vivo, referred to as "angiogenesis" and "vasculogenesis" (Risau 1997). Angiogenesis is the formation of new capillaries branching from preexisting blood vessels. To investigate this angiogenic process, an in vitro 3D angiogenesis model has been developed. In this model, hydrogels, such as collagen gel and fibrin gel, are formed in a culture dish, and ECs are seeded on the surface of the 3D hydrogel scaffold. ECs grow on the gel surface and finally form a confluent monolayer. When the cells are cultured with no growth factors, they maintain a confluent monolayer, which is similar to the ECs covering the luminal surface of blood vessels in vivo (step 1, Fig. 16.1a). However, when ECs are cultured and supplemented with angiogenic growth factors, such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), some ECs penetrate into the underlying gel to form vascular sprouts, which is the beginning of vascular formation (step 2, Fig. 16.1a). T...

show abstract

Reconstruction of hepatic stellate cell-incorporated liver capillary structures in small hepatocyte tri-culture using microporous membranes

Cited by 9 publications

References 35 publications

Human Stem Cell-Derived Endothelial-Hepatic Platform for Efficacy Testing of Vascular-Protective Metabolites from Nutraceuticals

Human Stem Cell-Derived Endothelial-Hepatic Platform for Efficacy Testing of Vascular-Protective Metabolites from Nutraceuticals

Microporous membrane-based liver tissue engineering for the reconstruction of three-dimensional functional liver tissues in vitro

Integrated Vascular Engineering: Vascularization of Reconstructed Tissue

Contact Info

Product

Resources

About