Vascularized subcutaneous human liver tissue from engineered hepatocyte/fibroblast sheets in mice

Sakai, Yusuke; Yamanouchi, Kaoru; Ohashi, Kazuhiko; Koike, Makiko; Utoh, Rie; Hasegawa, Hideko; Izumi, Mitsuru; Suematsu, Takashi; Soyama, Akihiko; Hidaka, Masaaki; Takatsuki, Mitsuhisa; Kuroki, Tamotsu; Eguchi, Susumu

doi:10.1016/j.biomaterials.2015.06.046

Cited by 58 publications

(62 citation statements)

References 38 publications

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“…While transplantation of hepatocyte or hepatocyte‐like cell‐sheets appears to be considered as an innovative therapeutic strategy for liver injuries and consequently liver diseases in small animal models, the presented results justify the application of these cell‐sheets to large animals and subsequently to clinical trials …”

Section: Conventional Versus Advanced Processing Technologies For LIVmentioning

confidence: 78%

“…Multilayered easy‐to‐handle human primary fibroblast/hepatocyte cell‐sheets have been engineered and have demonstrated high levels of hepatic‐specific functions, such as albumin and urea synthesis, and high potential for vascularization in vitro . After subcutaneous transplantation of these cocultured cell‐sheets into mice models, Sakai et al observed that those constructs are able to develop into vascularized liver‐like tissues possessing higher hepatic functions than from the hepatocyte‐only sheets.…”

Section: Conventional Versus Advanced Processing Technologies For LIVmentioning

confidence: 99%

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Advanced Biomaterials and Processing Methods for Liver Regeneration: State‐of‐the‐Art and Future Trends

Morais

Vieira

Zhao

et al. 2020

Adv Healthcare Materials

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Liver diseases contribute markedly to the global burden of mortality and disease. The limited organ disposal for orthotopic liver transplantation results in a continuing need for alternative strategies. Over the past years, important progress has been made in the field of tissue engineering (TE). Many of the early trials to improve the development of an engineered tissue construct are based on seeding cells onto biomaterial scaffolds. Nowadays, several TE approaches have been developed and are applied to one vital organ: the liver. Essential elements must be considered in liver TE—cells and culturing systems, bioactive agents or growth factors (GF), and biomaterials and processing methods. The potential of hepatocytes, mesenchymal stem cells, and others as cell sources is demonstrated. They need engineered biomaterial‐based scaffolds with perfect biocompatibility and bioactivity to support cell proliferation and hepatic differentiation as well as allowing extracellular matrix deposition and vascularization. Moreover, they require a microenvironment provided using conventional or advanced processing technologies in order to supply oxygen, nutrients, and GF. Herein the biomaterials and the conventional and advanced processing technologies, including cell‐sheets process, 3D bioprinting, and microfluidic systems, as well as the future trends in these major fields are discussed.

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Section: Conventional Versus Advanced Processing Technologies For LIVmentioning

confidence: 78%

Section: Conventional Versus Advanced Processing Technologies For LIVmentioning

confidence: 99%

Advanced Biomaterials and Processing Methods for Liver Regeneration: State‐of‐the‐Art and Future Trends

Morais

Vieira

Zhao

et al. 2020

Adv Healthcare Materials

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“…Hepatocyte cell sheets demonstrated robust expression of albumin as evaluated via immunohistochemistry; increases in protein production correlated with enhanced liver tissue volume as a result of layering multiple cell sheets (67). In addition to robust albumin and A1AT production, cell sheets derived from hepatocytes co-cultured with fibroblasts promoted enhanced vascularization after subcutaneous implantation when compared to hepatocyte-derived sheets (68). This scaffold-free co-culture technique could address the pressing need for vascularization after transplantation to ensure survival of engineered liver tissues.…”

Section: Non-mechanical Tissuesmentioning

confidence: 99%

The Self-Assembling Process and Applications in Tissue Engineering

Lee

Link

et al. 2017

Cold Spring Harb Perspect Med

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Tissue engineering strives to create neotissues capable of restoring function. Scaffold-free technologies have emerged that can recapitulate native tissue function without the use of an exogenous scaffold. This chapter will survey, in particular, the self-assembling and self-organization processes as scaffold-free techniques. Characteristics and benefits of each process are described, and key examples of tissues created using these scaffold-free processes are examined to provide guidance for future tissue engineering developments. This chapter aims to explore the potential of self-assembly and self-organization scaffold-free approaches, detailing the recent progress in the in vitro tissue engineering of biomimetic tissues with these methods, toward generating functional tissue replacements.

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“…These pre-vascularized cell sheets were subcutaneously transplanted and ultimately integrated into immunodeficient rats [48]. Another group used a similar approach to engineer pre-vascularized liver tissue composed of a layer of hepatocytes and a layer of fibroblasts, which integrated with the vasculature in the subcutaneous murine tissue [49]. Owing to the reproducibility of this approach and the ability to control cellular composition, this is a promising approach for the fabrication of thin vascularized tissue constructs for patch-based applications.…”

Section: In Vitro Approaches For Vascularizing Biomaterialsmentioning

confidence: 99%

Vascularization of three-dimensional engineered tissues for regenerative medicine applications

2016

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Engineering of three-dimensional (3D) tissues is a promising approach for restoring diseased or dysfunctional myocardium with a functional replacement. However, a major bottleneck in this field is the lack of efficient vascularization strategies, because tissue constructs produced in vitro require a constant flow of oxygen and nutrients to maintain viability and functionality. Compared to angiogenic cell therapy and growth factor treatment, bioengineering approaches such as spatial micropatterning, sacrificial materials, tissue decellularization, and 3D bioprinting enable the generation of more precisely controllable neovessel formation. In this review, we summarize the state-of-the-art approaches to develop 3D tissue engineered constructs with vasculature, and demonstrate how some of these techniques have been applied towards regenerative medicine for treatment of heart failure.

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Vascularized subcutaneous human liver tissue from engineered hepatocyte/fibroblast sheets in mice

Abstract: 1Subcutaneous liver tissue engineering is an attractive and minimally invasive approach used 2 for curative treat hepatic failure and inherited liver diseases. However, graft failure occurs

Cited by 58 publications

References 38 publications

Advanced Biomaterials and Processing Methods for Liver Regeneration: State‐of‐the‐Art and Future Trends

Advanced Biomaterials and Processing Methods for Liver Regeneration: State‐of‐the‐Art and Future Trends

The Self-Assembling Process and Applications in Tissue Engineering

Vascularization of three-dimensional engineered tissues for regenerative medicine applications

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