A Hepatic Scaffold from Decellularized Liver Tissue: Food for Thought

Croce, Stefania; Peloso, Andréa; Zoro, Tamara; Avanzini, Maria Antonietta; Cobianchi, Lorenzo

doi:10.3390/biom9120813

Cited by 51 publications

(42 citation statements)

References 143 publications

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“…Previous studies have shown that tissue-engineered livers are an attractive organ replacement solution for compensating the shortage of liver sources. Transplanting cells into a liver matrix made up of a decellularized scaffold that mimics the microstructure of native tissues is expected to provide a functional bionic liver [21][22][23][24][25][26][27]. Our study demonstrated that detergent perfusion through the portal vein created a translucent liver matrix while maintaining the native vasculature for adequate perfusion of constructs that were able to withstand physiological blood pressures.…”

Section: Discussionmentioning

confidence: 99%

Syndecan-4 promotes vascular beds formation in tissue engineered liver via thrombospondin 1

Chen

Huang

et al. 2020

Bioengineered

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Instantaneous blood coagulation after bioengineered liver transplantation is a major issue, and the key process in its prevention is the construction of the endothelial vascular bed on biomimetic scaffolds. However, the specific molecules involved in the regulation of the vascular bed formation remain unclear. Syndecan-4 is a type I transmembrane glycoprotein commonly expressed in the human body; its receptor has been reported as critical for optimal cell adhesion and initiation of intracellular signaling, indicating its promising application in vascular bed formation. In the current study, bioinformatics analysis and in vitro experiments were performed to evaluate whether syndecan-4 promoted endothelial cell migration and functional activation. Exogenous syndecan-4-overexpressing endothelial cells were perfused into the decellularized liver scaffold, which was assessed by Masson's trichrome staining. Western blotting and qRT-PCR were used to evaluate the effects of syndecan-4 on the thrombospondin 1 (THBS1) stability. We found that syndecan-4 promoted the adhesion of vascular endothelial cells and facilitated cell migration and angiogenesis. Furthermore, syndecan-4 overexpression resulted in a well-aligned endothelium on the decellularized liver scaffolds. Mechanistically, syndecan-4 destabilized THBS1 at the protein level. Therefore, our data revealed that syndecan-4 promoted the biological activity of endothelial cells on the bionic liver vascular bed through THBS1. These findings provide scientific evidences for solving transient blood coagulation after bionic liver transplantation.

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Section: Discussionmentioning

confidence: 99%

Syndecan-4 promotes vascular beds formation in tissue engineered liver via thrombospondin 1

Chen

Huang

et al. 2020

Bioengineered

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“…The results obtained demonstrated that it was possible to in vitro re-create a tissue-engineered trachea with mechanical properties that allow normal functioning, providing successful treatment for patients [ 166 ]. Following this, many studies using a single type of tissue-specific stem cells [ 158 , 170 , 181 , 182 , 183 , 184 , 185 ] or induced pluripotent cells [ 185 , 186 , 187 , 188 ] were carried out, and others are currently ongoing, in order to identify the best 3D supports able to boost cell differentiation and successfully produce in vitro functional tissues and organs for future possible transplantation. In parallel, both synthetic and biological scaffolds were repopulated with terminally differentiated cells, including fibroblasts [ 155 ], mature hepatocytes [ 189 , 190 , 191 ], and pancreatic endocrine [ 192 , 193 , 194 ], cardiac [ 195 ], and ovarian cells [ 196 ].…”

Section: Tissue and Organ Regeneration Approachesmentioning

confidence: 99%

Current Advances in 3D Tissue and Organ Reconstruction

Pennarossa

Arcuri

Iorio

et al. 2021

IJMS

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Bi-dimensional culture systems have represented the most used method to study cell biology outside the body for over a century. Although they convey useful information, such systems may lose tissue-specific architecture, biomechanical effectors, and biochemical cues deriving from the native extracellular matrix, with significant alterations in several cellular functions and processes. Notably, the introduction of three-dimensional (3D) platforms that are able to re-create in vitro the structures of the native tissue, have overcome some of these issues, since they better mimic the in vivo milieu and reduce the gap between the cell culture ambient and the tissue environment. 3D culture systems are currently used in a broad range of studies, from cancer and stem cell biology, to drug testing and discovery. Here, we describe the mechanisms used by cells to perceive and respond to biomechanical cues and the main signaling pathways involved. We provide an overall perspective of the most recent 3D technologies. Given the breadth of the subject, we concentrate on the use of hydrogels, bioreactors, 3D printing and bioprinting, nanofiber-based scaffolds, and preparation of a decellularized bio-matrix. In addition, we report the possibility to combine the use of 3D cultures with functionalized nanoparticles to obtain highly predictive in vitro models for use in the nanomedicine field.

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“…Дефицит донорских органов для трансплантации печени при лечении терминальных стадий печеночной недостаточности диктует необходимость разработки альтернативных методов, к которым относятся технологии тканевой инженерии и регенеративной медицины [1,2].…”

Section: Introductionunclassified

“…Отметим, что взаимодействие клеток с полученным тканеспецифическим матриксом изучено не было. 1,3 , M.Yu. Shagidulin 1,3 , V.I.…”

Section: Introductionunclassified

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Experimental approaches to creating a tissue-specific matrix for a bioartificial liver

Григорьев

Басок

Kirillova

et al. 2020

RJTAO

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Shortage of donor organs for liver transplantation in the treatment of end-stage liver disease dictates the need to develop alternative methods that include technologies on tissue engineering and regenerative medicine. Objective: to study the ability of a tissue-specific matrix from decellularized human liver fragments (DHLF) to maintain adhesion and proliferation of human adipose tissue-derived mesenchymal stem cells (hAT-MSCs) and HepG2 under static conditions and in a flow-through bioreactor. Materials and methods. Treatment with surfactants (SAS) – sodium dodecyl sulfate, Triton X-100 – followed by exposure to DNase was used for decellularization of human liver fragments (no more than 8 mm3). Biochemical screening included the determination of DNA quantity in the test samples. Efficiency of surfactant washing was assessed by the cytotoxicity of the matrix in the NIH 3T3 fibroblast culture. Viability and metabolic activity of cells were assessed via vital staining with a complex of fluorescent dyes LIVE/DEAD ® and PrestoBlue™ (Invitrogen, USA). Morphological examination of the liver cell-engineered constructs was carried out through histological staining and scanning electron microscopy with lanthanide contrast. Results. It was shown that the liver decellularization method used allows to obtain a biocompatible matrix with a residual DNA quantity <1%, which is capable of maintaining adhesion and proliferation of hAT-MSCs and HepG2. On day 7 of cultivation in the bioreactor, there was formation of a single conglomerate of the DHLF matrix with numerous groups of viable cells with a high nuclear-cytoplasmic ratio. The urea content in the culture medium is 1.5 ± 0.1 mmol/L, exceeding that of samples obtained under static conditions. This indicates the metabolic activity of HepG2 in the composition of the obtained culture systems. It was shown that constant flow of the culture medium in the perfusion bioreactor increased the proliferative activity of HepG2 and allowed to provide a more uniform colonization by matrix cells in comparison with static cultivation conditions. Conclusion. The conditions for uniform colonization of DHLFs in a flow-through bioreactor with cell cultures were established. The ability of the matrix to maintain adhesion and proliferation of hADSCs and HepG2 for 11 days indicates that it could be used in liver tissue engineering.

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A Hepatic Scaffold from Decellularized Liver Tissue: Food for Thought

Cited by 51 publications

References 143 publications

Syndecan-4 promotes vascular beds formation in tissue engineered liver via thrombospondin 1

Syndecan-4 promotes vascular beds formation in tissue engineered liver via thrombospondin 1

Current Advances in 3D Tissue and Organ Reconstruction

Experimental approaches to creating a tissue-specific matrix for a bioartificial liver

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