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Chi KY, Kim G, Son JS, Han J, Kim JH. Recent Advances in Three-Dimensional In Vitro Models for Studies of Liver Fibrosis. Tissue Eng Regen Med 2025:10.1007/s13770-025-00719-8. [PMID: 40358834 DOI: 10.1007/s13770-025-00719-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2025] [Revised: 02/02/2025] [Accepted: 03/11/2025] [Indexed: 05/15/2025] Open
Abstract
BACKGROUND Liver fibrosis is a reversible but complex pathological condition associated with chronic liver diseases, affecting over 1.5 billion people worldwide. It is characterized by excessive extracellular matrix deposition resulting from sustained liver injury, often advancing to cirrhosis and cancer. As its progression involves various cell types and pathogenic factors, understanding the intricate mechanisms is essential for the development of effective therapies. In this context, extensive efforts have been made to establish three-dimensional (3D) in vitro platforms that mimic the progression of liver fibrosis. METHODS This review outlines the pathophysiology of liver fibrosis and highlights recent advancements in 3D in vitro liver models, including spheroids, organoids, assembloids, bioprinted constructs, and microfluidic systems. It further assesses their biological relevance, with particular focus on their capacity to reproduce fibrosis-related characteristics. RESULTS 3D in vitro liver models offer significant advantages over conventional two-dimensional cultures. Although each model exhibits unique strengths, they collectively recapitulate key fibrotic features, such as extracellular matrix remodeling, hepatic stellate cell activation, and collagen deposition, in a physiologically relevant 3D setting. In particular, multilineage liver organoids and assembloids integrate architectural complexity with scalability, enabling deeper mechanistic insights and supporting therapeutic evaluation with improved translational relevance. CONCLUSION 3D in vitro liver models represent a promising strategy to bridge the gap between in vitro studies and in vivo realities by faithfully replicating liver-specific architecture and microenvironments. With enhanced reproducibility through standardized protocols, these models hold great potential for advancing drug discovery and facilitating the development of personalized therapies for liver fibrosis.
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Affiliation(s)
- Kyun Yoo Chi
- Laboratory of Stem Cells and Tissue Regeneration, Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, 02841, South Korea
| | - Gyeongmin Kim
- Laboratory of Stem Cells and Tissue Regeneration, Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, 02841, South Korea
| | - Jeong Sang Son
- User Convenience Technology R&D Department, Korea Institute of Industrial Technology (KITECH), Ansan, 15588, South Korea
| | - Jiyou Han
- Department of Biomedical and Chemical Sciences, Hyupsung University, Hwasung-Si, 18330, South Korea
| | - Jong-Hoon Kim
- Laboratory of Stem Cells and Tissue Regeneration, Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, 02841, South Korea.
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Derakhshan R, Ahmadian MT. Experimental and numerical investigation of waterjet interaction with liver in connection with surgical technique. Heliyon 2024; 10:e36454. [PMID: 39281641 PMCID: PMC11396041 DOI: 10.1016/j.heliyon.2024.e36454] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2023] [Revised: 07/15/2024] [Accepted: 08/15/2024] [Indexed: 09/18/2024] Open
Abstract
Hepatectomy, or liver resection, is a process by which through surgery part or all of the liver is removed. In this operation, less bleeding, negligible damage and fast removal are the most important requirements. Surgery through waterjet is one of the most efficient techniques which is widely used in hepatectomy. Some clinical studies are conducted to investigate waterjet method in liver resection. In the present study interaction of waterjet with liver during the process of the surgery is investigated in terms of mechanical engineering. For this purpose, a system of waterjet is designed to consider the interaction of waterjet with liver at different nozzle diameter and velocities. For validation, SPH-FEM model is used to analyze waterjet interaction with hyperelastic liver. In this model, liver cutting is simulated using element deletion defined by a subroutine code based on maximum principal strain criterion. Depth of cut along with degraded volume are measured experimentally and compared with simulated method. Results show that good agreement exists between experimental and simulation finding. By comparing depth of cut in the experimental and simulation results, it can be seen that liver behavior changes from brittle to ductile by increasing waterjet velocity during the experimental tests. For the simulation, maximum principal strain threshold is set to be between 0.1 and 0.4. However, the best agreement between experimental and simulation results exists at maximum principal strain threshold equal to 0.2. The findings can help surgeons to find the best working range of waterjet device and the most efficient operation.
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Affiliation(s)
- R Derakhshan
- School of Mechanical Engineering, Sharif University of Technology, Tehran, Iran
| | - M T Ahmadian
- School of Mechanical Engineering, Sharif University of Technology, Center of Excellence in Design, Robotic and Automation, Tehran, Iran
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3
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Kakabadze Z, Paresishvili T. Intravital tumor decellularization as a new approach to cancer treatment. Am J Cancer Res 2023; 13:4192-4207. [PMID: 37818079 PMCID: PMC10560955] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2023] [Accepted: 08/08/2023] [Indexed: 10/12/2023] Open
Abstract
This study demonstrates the possibility of tumor decellularization in living animals. Subcutaneous Ehrlich tumor induced by isolated Ehrlich ascitic carcinoma cells in mice was used as a model. The study also presents methods for ex vivo decellularization of human gastric adenocarcinoma (HGA) and hepatocellular carcinoma (HCC) induced by diethylnitrosamine (DEN) in rat. Sodium dodecyl sulfate (SDS) and Triton X-100 were used as detergents for tumor decellularization. The detergents for HGA and HCC were administered through organ vessels. For intravital decellularization of Ehrlich's subcutaneous tumor, detergents were injected directly into the tumor parenchyma. The results of the study showed that the effectiveness of tumor decellularization using SDS and Triton X-100 depended on the size, structure, stiffness and density of the tumor, as well as on the concentration, route and speed of detergent administration. The study also showed that an hour after the initiation of decellularization, the central part of Ehrlich's tumor changed the color, and after three hours, it completely acquired a translucent white color. Chemical contamination of tissues surrounding the tumor with the detergents was not observed. Histological studies showed the complete absence of all cellular components of Ehrlich's tumor and a slightly deformed extracellular matrix (ECM). There were no loco-regional recurrences or metastases of Ehrlich's tumor within 150 days after decellularization. The developed intravital decellularization method allows the effective removal of the cellular components and the DNA content of Ehrlich's subcutaneous tumor without compromising animal health. Additionally, this method can destroy tumor ECM, which will significantly improve the delivery of anticancer drugs to the tumor cells. However, more detailed and extensive studies are needed to develop an in vivo technique for isolated decellularization of the tumor or a part of the organ with the tumor. It is also necessary to identify less toxic decellularization agents and to develop the most efficient route for their delivery to the tumor cells.
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Affiliation(s)
- Zurab Kakabadze
- Department of Clinical Anatomy, Tbilisi State Medical University 0186 Tbilisi, Georgia
| | - Teona Paresishvili
- Department of Clinical Anatomy, Tbilisi State Medical University 0186 Tbilisi, Georgia
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4
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Mir TA, Nakamura M, Sakai S, Iwanaga S, Wani SI, Alzhrani A, Arai K, Mir BA, Kazmi S, Assiri AM, Broering DC. Mammalian-specific decellularized matrices derived bioink for bioengineering of liver tissue analogues: A review. Int J Bioprint 2023; 9:714. [PMID: 37273993 PMCID: PMC10236352 DOI: 10.18063/ijb.714] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Accepted: 01/18/2023] [Indexed: 06/06/2023] Open
Abstract
The absolute shortage of compatible liver donors and the growing number of potential recipients have led scientists to explore alternative approaches to providing tissue/ organ substitutes from bioengineered sources. Bioartificial regeneration of a fully functional tissue/organ replacement is highly dependent on the right combination of engineering tools, biological principles, and materiobiology horizons. Over the past two decades, remarkable achievements have been made in hepatic tissue engineering by converging various advanced interdisciplinary research approaches. Three-dimensional (3D) bioprinting has arisen as a promising state-of-the-art tool with strong potential to fabricate volumetric liver tissue/organ equivalents using viscosity- and degradation-controlled printable bioinks composed of hydrous microenvironments, and formulations containing living cells and associated supplements. Source of origin, biophysiochemical, or thermomechanical properties and crosslinking reaction kinetics are prerequisites for ideal bioink formulation and realizing the bioprinting process. In this review, we delve into the forecast of the potential future utility of bioprinting technology and the promise of tissue/organ- specific decellularized biomaterials as bioink substrates. Afterward, we outline various methods of decellularization, and the most relevant studies applying decellularized bioinks toward the bioengineering of in vitro liver models. Finally, the challenges and future prospects of decellularized material-based bioprinting in the direction of clinical regenerative medicine are presented to motivate further developments.
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Affiliation(s)
- Tanveer Ahmad Mir
- Transplant Research and Innovation Department, Tissue/Organ Bioengineering & BioMEMS Laboratory, Organ Transplant Centre of Excellence, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, KSA
| | - Makoto Nakamura
- Division of Biomedical System Engineering, Graduate School of Science and Engineering, University of Toyama, Toyama 930-8555, Japan
| | - Shinji Sakai
- Division of Chemical Engineering, Department of Materials Engineering Science, Graduate School of Engineering Science, Osaka University, Toyonaka, Osaka 560-8531, Japan
| | - Shintaroh Iwanaga
- Division of Biomedical System Engineering, Graduate School of Science and Engineering, University of Toyama, Toyama 930-8555, Japan
| | - Shadil Ibrahim Wani
- Division of Biomedical System Engineering, Graduate School of Science and Engineering, University of Toyama, Toyama 930-8555, Japan
| | - Alaa Alzhrani
- Transplant Research and Innovation Department, Tissue/Organ Bioengineering & BioMEMS Laboratory, Organ Transplant Centre of Excellence, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, KSA
- Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, KSA
- College of Medicine, Alfaisal University, Riyadh 11211, KSA
| | - Kenichi Arai
- Department of Clinical Biomaterial Applied Science, Faculty of Medicine, University of Toyama, Toyama 930-0194, Japan
| | - Bilal Ahmed Mir
- Division of Intellectual Information Engineering, Graduate School of Science and Engineering, University of Toyama, Toyama 930-8555, Japan
| | - Shadab Kazmi
- Transplant Research and Innovation Department, Tissue/Organ Bioengineering & BioMEMS Laboratory, Organ Transplant Centre of Excellence, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, KSA
- Department of Child Health, School of Medicine, University of Missouri, Columbia, USA
| | - Abdullah M. Assiri
- Transplant Research and Innovation Department, Tissue/Organ Bioengineering & BioMEMS Laboratory, Organ Transplant Centre of Excellence, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, KSA
- College of Medicine, Alfaisal University, Riyadh 11211, KSA
| | - Dieter C. Broering
- Transplant Research and Innovation Department, Tissue/Organ Bioengineering & BioMEMS Laboratory, Organ Transplant Centre of Excellence, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, KSA
- College of Medicine, Alfaisal University, Riyadh 11211, KSA
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Yoshida T, Kobayashi M, Uomoto S, Ohshima K, Hara E, Katoh Y, Takahashi N, Harada T, Usui T, Elbadawy M, Shibutani M. The potential of organoids in toxicologic pathology: role of toxicologic pathologists in in vitro chemical hepatotoxicity assessment. J Toxicol Pathol 2022; 35:225-235. [PMID: 35832897 PMCID: PMC9256002 DOI: 10.1293/tox.2022-0017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2022] [Accepted: 04/28/2022] [Indexed: 11/19/2022] Open
Abstract
The development of in vitro toxicity assessment methods using cultured cells has gained popularity for promoting animal welfare in animal experiments. Herein, we briefly discuss the current status of hepatoxicity assessment using human- and rat-derived hepatocytes; we focus on the liver organoid method, which has been extensively studied in recent years, and discuss how toxicologic pathologists can use their knowledge and experience to contribute to the development of in vitro chemical hepatotoxicity assessment methods for drugs, pesticides, and chemicals. We also propose how toxicological pathologists should assess toxicity regarding the putative distribution of undifferentiated and differentiated cells in the organoid when liver organoids are observed in hematoxylin and eosin-stained specimens. This was done while considering the usefulness and limitations of in vitro studies for toxicologic pathology assessment.
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Affiliation(s)
- Toshinori Yoshida
- Laboratory of Veterinary Pathology, Cooperative Department
of Veterinary Medicine, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho,
Fuchu-shi, Tokyo 183-8509, Japan
| | - Mio Kobayashi
- Laboratory of Veterinary Pathology, Cooperative Department
of Veterinary Medicine, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho,
Fuchu-shi, Tokyo 183-8509, Japan
- Cooperative Division of Veterinary Sciences, Tokyo
University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509,
Japan
| | - Suzuka Uomoto
- Laboratory of Veterinary Pathology, Cooperative Department
of Veterinary Medicine, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho,
Fuchu-shi, Tokyo 183-8509, Japan
| | - Kanami Ohshima
- Laboratory of Veterinary Pathology, Cooperative Department
of Veterinary Medicine, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho,
Fuchu-shi, Tokyo 183-8509, Japan
| | - Emika Hara
- Laboratory of Veterinary Pathology, Cooperative Department
of Veterinary Medicine, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho,
Fuchu-shi, Tokyo 183-8509, Japan
| | - Yoshitaka Katoh
- Laboratory of Pathology, Toxicology Division, The Institute
of Environmental Toxicology, 4321 Uchimoriya-machi, Joso-shi, Ibaraki 303-0043,
Japan
| | - Naofumi Takahashi
- Laboratory of Pathology, Toxicology Division, The Institute
of Environmental Toxicology, 4321 Uchimoriya-machi, Joso-shi, Ibaraki 303-0043,
Japan
| | - Takanori Harada
- Laboratory of Pathology, Toxicology Division, The Institute
of Environmental Toxicology, 4321 Uchimoriya-machi, Joso-shi, Ibaraki 303-0043,
Japan
| | - Tatsuya Usui
- Laboratory of Veterinary Pharmacology, Cooperative
Department of Veterinary Medicine, Tokyo University of Agriculture and Technology, 3-5-8
Saiwai-cho, Fuchu-shi, Tokyo 183-8509, Japan
| | - Mohamed Elbadawy
- Laboratory of Veterinary Pharmacology, Cooperative
Department of Veterinary Medicine, Tokyo University of Agriculture and Technology, 3-5-8
Saiwai-cho, Fuchu-shi, Tokyo 183-8509, Japan
- Department of Pharmacology, Faculty of Veterinary Medicine,
Benha University, 13736 Moshtohor, Toukh, Elqaliobiya, Egypt
| | - Makoto Shibutani
- Laboratory of Veterinary Pathology, Cooperative Department
of Veterinary Medicine, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho,
Fuchu-shi, Tokyo 183-8509, Japan
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6
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Ergun C, Parmaksiz M, Vurat MT, Elçin AE, Elçin YM. Decellularized liver ECM-based 3D scaffolds: Compositional, physical, chemical, rheological, thermal, mechanical, and in vitro biological evaluations. Int J Biol Macromol 2022; 200:110-123. [PMID: 34971643 DOI: 10.1016/j.ijbiomac.2021.12.086] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2021] [Revised: 12/01/2021] [Accepted: 12/15/2021] [Indexed: 12/18/2022]
Abstract
The extracellular matrix (ECM) is involved in many critical cellular interactions through its biological macromolecules. In this study, a macroporous 3D scaffold originating from decellularized bovine liver ECM (dL-ECM), with defined compositional, physical, chemical, rheological, thermal, mechanical, and in vitro biological properties was developed. First, protocols were determined that effectively remove cells and DNA while ECM retains biological macromolecules collagen, elastin, sGAGs in tissue. Rheological analysis revealed the elastic properties of pepsin-digested dL-ECM. Then, dL-ECM hydrogel was neutralized, molded, formed into macroporous (~100-200 μm) scaffolds in aqueous medium at 37 °C, and lyophilized. The scaffolds had water retention ability, and were mechanically stable for at least 14 days in the culture medium. The findings also showed that increasing the dL-ECM concentration from 10 mg/mL to 20 mg/mL resulted in a significant increase in the mechanical strength of the scaffolds. The hemolysis test revealed high in vitro hemocompatibility of the dL-ECM scaffolds. Studies investigating the viability and proliferation status of human adipose stem cells seeded over a 2-week culture period have demonstrated the suitability of dL-ECM scaffolds as a cell substrate. Prospective studies may reveal the extent to which 3D dL-ECM sponges have the potential to create a biomimetic environment for cells.
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Affiliation(s)
- Can Ergun
- Tissue Engineering, Biomaterials and Nanobiotechnology Laboratory, Ankara University Faculty of Science, and Stem Cell Institute, Ankara, Turkey
| | - Mahmut Parmaksiz
- Tissue Engineering, Biomaterials and Nanobiotechnology Laboratory, Ankara University Faculty of Science, and Stem Cell Institute, Ankara, Turkey
| | - Murat Taner Vurat
- Tissue Engineering, Biomaterials and Nanobiotechnology Laboratory, Ankara University Faculty of Science, and Stem Cell Institute, Ankara, Turkey
| | - Ayşe Eser Elçin
- Tissue Engineering, Biomaterials and Nanobiotechnology Laboratory, Ankara University Faculty of Science, and Stem Cell Institute, Ankara, Turkey
| | - Yaşar Murat Elçin
- Tissue Engineering, Biomaterials and Nanobiotechnology Laboratory, Ankara University Faculty of Science, and Stem Cell Institute, Ankara, Turkey; Biovalda Health Technologies, Inc., Ankara, Turkey.
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7
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Morales-Guerrero NA, Varela-Echavarría A, Lozano Flores C, Vázquez-Cuevas FG, Velázquez-Miranda E, Reyes-López JV, García-Solís P, Solís-S JC, Hernández-Montiel HL. A new strategy for the decellularization of whole organs by hydrostatic pressure. Biotechnol Prog 2022; 38:e3248. [PMID: 35201677 DOI: 10.1002/btpr.3248] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2021] [Revised: 02/21/2022] [Accepted: 02/23/2022] [Indexed: 11/06/2022]
Abstract
Tissue engineering has been able to develop novel decellularization-recellularization techniques, which facilitates the research for the generation of functional organs. This is based in the initial obtention of the organ's extracellular matrix (ECM). Therefore, any improvement in the decellularization process would have a positive impact in the results of the recellularization process. Nevertheless, commonly the methods and equipment employed for this process are expensive and thus limit the access of this technique to various research groups globally. AIM To develop a decellularization technique with the exclusive use of hydrostatic pressure of detergent solutions, to have an easily accessible and low-cost technique that meets the basic requirements of acellularity and functionality of the ECM. METHODS This experimental study was performed in 10 male Wistar rats, obtaining the liver to carry out serial washes, with 1, 2 and 3% Triton X-100 solutions and 0.1% SDS. The washes were performed by using a Gravity Perfusion System (GPS), which assured us a continuous hydrostatic pressure of 7.5 mmHg. The obtained ECM was processed using stains and immunostaining to determine the residual cell content and preservation of its components. RESULTS The staining showed a removal of cellular and nuclear components of approximately 97% of the acellular ECM, with an adequate three-dimensional pattern of collagen and proteoglycans. Furthermore, the acellular ECM allowed the viability of a primary hepatocyte culture. CONCLUSIONS The use of the GPS decellularization technique allowed us to obtain an acellular and functional ECM, drastically reducing experimentation costs. This article is protected by copyright. All rights reserved.
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Affiliation(s)
- Nelly A Morales-Guerrero
- Department of Biomedical Research, School of Medicine, Autonomous University of Queretaro, Qro., Mexico
| | | | - Carlos Lozano Flores
- Institute of Neurobiology, National Autonomous University of Mexico, Qro., Mexico
| | | | | | - Julián V Reyes-López
- Laboratory of Neurobiology and Cellular Bioengineering, Neurodiagnostic and Rehabilitation Unit "Dr. Moisés López González ", Faculty of Natural Sciences, Autonomous University of Querétaro
| | - Pablo García-Solís
- Department of Biomedical Research, School of Medicine, Autonomous University of Queretaro, Qro., Mexico
| | - Juan Carlos Solís-S
- Department of Biomedical Research, School of Medicine, Autonomous University of Queretaro, Qro., Mexico
| | - Hebert Luis Hernández-Montiel
- Laboratory of Neurobiology and Cellular Bioengineering, Neurodiagnostic and Rehabilitation Unit "Dr. Moisés López González ", Faculty of Natural Sciences, Autonomous University of Querétaro
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8
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Dai Q, Jiang W, Huang F, Song F, Zhang J, Zhao H. Recent Advances in Liver Engineering With Decellularized Scaffold. Front Bioeng Biotechnol 2022; 10:831477. [PMID: 35223793 PMCID: PMC8866951 DOI: 10.3389/fbioe.2022.831477] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2021] [Accepted: 01/24/2022] [Indexed: 12/02/2022] Open
Abstract
Liver transplantation is currently the only effective treatment for patients with end-stage liver disease; however, donor liver scarcity is a notable concern. As a result, extensive endeavors have been made to diversify the source of donor livers. For example, the use of a decellularized scaffold in liver engineering has gained considerable attention in recent years. The decellularized scaffold preserves the original orchestral structure and bioactive chemicals of the liver, and has the potential to create a de novo liver that is fit for transplantation after recellularization. The structure of the liver and hepatic extracellular matrix, decellularization, recellularization, and recent developments are discussed in this review. Additionally, the criteria for assessment and major obstacles in using a decellularized scaffold are covered in detail.
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Affiliation(s)
- Qingqing Dai
- Department of Hepatopancreatobiliary Surgery and Organ Transplantation Center, Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China
- Department of Internal Medicine IV (Gastroenterology, Hepatology, and Infectious Diseases), Jena University Hospital, Jena, Germany
| | - Wei Jiang
- Department of Burns, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Fan Huang
- Department of Hepatopancreatobiliary Surgery and Organ Transplantation Center, Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Fei Song
- Department of Urology, Jena University Hospital, Jena, Germany
| | - Jiqian Zhang
- Department of Anesthesiology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
- *Correspondence: Jiqian Zhang, ; Hongchuan Zhao,
| | - Hongchuan Zhao
- Department of Hepatopancreatobiliary Surgery and Organ Transplantation Center, Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China
- *Correspondence: Jiqian Zhang, ; Hongchuan Zhao,
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9
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Patarashvili L, Gvidiani S, Azmaipharashvili E, Tsomaia K, Sareli M, Kordzaia D, Chanukvadze I. Porta-caval fibrous connections - the lesser-known structure of intrahepatic connective-tissue framework: A unified view of liver extracellular matrix. World J Hepatol 2021; 13:1484-1493. [PMID: 34904025 PMCID: PMC8637665 DOI: 10.4254/wjh.v13.i11.1484] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Revised: 05/17/2021] [Accepted: 08/30/2021] [Indexed: 02/06/2023] Open
Abstract
Knowledge about the connective-tissue framework of the liver is not systematized, the terminology is inconsistent and some perspectives on the construction of the hepatic matrix components are contradictory. In addition, until the last two decades of the 20th century, the connective-tissue sheaths of the portal tracts and the hepatic veins were considered to be independent from each other in the liver and that they do not make contact with each other. The results of the research carried out by Professor Shalva Toidze and his colleagues started in the 1970s in the Department of Operative Surgery and Topographic Anatomy at the Tbilisi State Medical Institute have changed this perception. In particular, Chanukvadze I showed that in some regions where they intersect with each other, the connective tissue sheaths of the large portal complexes and hepatic veins fuse. The areas of such fusion are called porta-caval fibrous connections (PCFCs). This opinion review aims to promote a systematic understanding of the hepatic connective-tissue skeleton and to demonstrate the hitherto underappreciated PCFC as a genuine structure with high biological and clinical significance. The components of the liver connective-tissue framework - the capsules, plates, sheaths, covers - are described, and their intercommunication is discussed. The analysis of the essence of the PCFC and a description of its various forms are provided. It is also mentioned that analogs of different forms of PCFC are found in different mammals.
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Affiliation(s)
- Leila Patarashvili
- Department of Clinical Anatomy and Operative Surgery, Ivane Javakhishvili Tbilisi State University, Tbilisi 0159, Georgia
| | - Salome Gvidiani
- Faculty of Medicine, Ivane Javakhishvili Tbilisi State University, Tbilisi 0159, Georgia
| | - Elza Azmaipharashvili
- Faculty of Medicine, Ivane Javakhishvili Tbilisi State University, Tbilisi 0159, Georgia
| | - Keti Tsomaia
- Clinical Anatomy and Experimental Modeling, Institute of Morphology, Ivane Javakhishvili Tbilisi State University, Tbilisi 0159, Georgia
| | - Marom Sareli
- Department of Surgical Oncology (Surgery C), Chaim Sheba Medical Center at HaShomer, Ramat Gan, Tel Aviv 52621, Israel
| | - Dimitri Kordzaia
- Department of Clinical Anatomy and Operative Surgery, Ivane Javakhishvili Tbilisi State University, Tbilisi 0159, Georgia.
| | - Ilia Chanukvadze
- Faculty of Medicine, Tbilisi State Medical University, Tbilsi 0177, Georgia
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