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Liu S, Cheng C, Zhu L, Zhao T, Wang Z, Yi X, Yan F, Wang X, Li C, Cui T, Yang B. Liver organoids: updates on generation strategies and biomedical applications. Stem Cell Res Ther 2024; 15:244. [PMID: 39113154 PMCID: PMC11304926 DOI: 10.1186/s13287-024-03865-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2024] [Accepted: 07/27/2024] [Indexed: 08/10/2024] Open
Abstract
The liver is the most important metabolic organ in the body. While mouse models and cell lines have further deepened our understanding of liver biology and related diseases, they are flawed in replicating key aspects of human liver tissue, particularly its complex structure and metabolic functions. The organoid model represents a major breakthrough in cell biology that revolutionized biomedical research. Organoids are in vitro three-dimensional (3D) physiological structures that recapitulate the morphological and functional characteristics of tissues in vivo, and have significant advantages over traditional cell culture methods. In this review, we discuss the generation strategies and current advances in the field focusing on their application in regenerative medicine, drug discovery and modeling diseases.
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Affiliation(s)
- Sen Liu
- Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang, 110016, China
- State Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Tianjin Institute of Pharmaceutical Research, Tianjin, 300301, China
| | | | - Liuyang Zhu
- First Central Clinical College of Tianjin Medical University, Tianjin, 300192, China
| | - Tianyu Zhao
- State Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Tianjin Institute of Pharmaceutical Research, Tianjin, 300301, China
| | - Ze Wang
- State Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Tianjin Institute of Pharmaceutical Research, Tianjin, 300301, China
- Research Unit for Drug Metabolism, Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Xiulin Yi
- State Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Tianjin Institute of Pharmaceutical Research, Tianjin, 300301, China
- Research Unit for Drug Metabolism, Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Fengying Yan
- State Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Tianjin Institute of Pharmaceutical Research, Tianjin, 300301, China
- Research Unit for Drug Metabolism, Chinese Academy of Medical Sciences, Beijing, 100730, China
| | - Xiaoliang Wang
- State Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Tianjin Institute of Pharmaceutical Research, Tianjin, 300301, China
| | - Chunli Li
- Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang, 110016, China.
| | - Tao Cui
- State Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Tianjin Institute of Pharmaceutical Research, Tianjin, 300301, China.
- Research Unit for Drug Metabolism, Chinese Academy of Medical Sciences, Beijing, 100730, China.
| | - Baofeng Yang
- Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang, 110016, China.
- School of Pharmacy, Harbin Medical University, Harbin, 150081, China.
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2
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Telles-Silva KA, Pacheco L, Chianca F, Komatsu S, Chiovatto C, Zatz M, Goulart E. iPSC-derived cells for whole liver bioengineering. Front Bioeng Biotechnol 2024; 12:1338762. [PMID: 38384436 PMCID: PMC10879941 DOI: 10.3389/fbioe.2024.1338762] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2023] [Accepted: 01/08/2024] [Indexed: 02/23/2024] Open
Abstract
Liver bioengineering stands as a prominent alternative to conventional hepatic transplantation. Through liver decellularization and/or bioprinting, researchers can generate acellular scaffolds to overcome immune rejection, genetic manipulation, and ethical concerns that often accompany traditional transplantation methods, in vivo regeneration, and xenotransplantation. Hepatic cell lines derived from induced pluripotent stem cells (iPSCs) can repopulate decellularized and bioprinted scaffolds, producing an increasingly functional organ potentially suitable for autologous use. In this mini-review, we overview recent advancements in vitro hepatocyte differentiation protocols, shedding light on their pivotal role in liver recellularization and bioprinting, thereby offering a novel source for hepatic transplantation. Finally, we identify future directions for liver bioengineering research that may allow the implementation of these systems for diverse applications, including drug screening and liver disease modeling.
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Affiliation(s)
- Kayque Alves Telles-Silva
- Human Genome and Stem-Cell Research Center (HUG-CEL), Institute of Biosciences, University of Sao Paulo, Sao Paulo, Brazil
- Department of Pharmaceutical Chemistry, Small Molecule Discovery Center, Genentech Hall, University of California, San Francisco, San Francisco, CA, United States
| | - Lara Pacheco
- Human Genome and Stem-Cell Research Center (HUG-CEL), Institute of Biosciences, University of Sao Paulo, Sao Paulo, Brazil
| | - Fernanda Chianca
- Human Genome and Stem-Cell Research Center (HUG-CEL), Institute of Biosciences, University of Sao Paulo, Sao Paulo, Brazil
| | - Sabrina Komatsu
- Human Genome and Stem-Cell Research Center (HUG-CEL), Institute of Biosciences, University of Sao Paulo, Sao Paulo, Brazil
| | - Caroline Chiovatto
- Human Genome and Stem-Cell Research Center (HUG-CEL), Institute of Biosciences, University of Sao Paulo, Sao Paulo, Brazil
| | - Mayana Zatz
- Human Genome and Stem-Cell Research Center (HUG-CEL), Institute of Biosciences, University of Sao Paulo, Sao Paulo, Brazil
| | - Ernesto Goulart
- Human Genome and Stem-Cell Research Center (HUG-CEL), Institute of Biosciences, University of Sao Paulo, Sao Paulo, Brazil
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Song Y, Lu Z, Shu W, Xiang Z, Wang Z, Wei X, Xu X. Arouse potential stemness: Intrinsic and acquired stem cell therapeutic strategies for advanced liver diseases. CELL INSIGHT 2023; 2:100115. [PMID: 37719773 PMCID: PMC10502372 DOI: 10.1016/j.cellin.2023.100115] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/08/2023] [Revised: 08/10/2023] [Accepted: 08/10/2023] [Indexed: 09/19/2023]
Abstract
Liver diseases are a major health issue, and prolonged liver injury always progresses. Advanced liver disorders impair liver regeneration. Millions of patients die yearly worldwide, even with the available treatments of liver transplantation and artificial liver support system. With its abundant cell resources and significant differentiative potential, stem cell therapy is a viable treatment for various disorders and offers hope to patients waiting for orthotopic liver transplantation. Considering such plight, stem cell therapeutic strategies deliver hope to the patients. Moreover, we conclude intrinsic and acquired perspectives based on stem cell sources. The properties and therapeutic uses of these stem cells' specific types or sources were then reviewed. Owing to the recent investigations of the above cells, a safe and effective therapy will emerge for advanced liver diseases soon.
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Affiliation(s)
- Yisu Song
- Department of Hepatobiliary and Pancreatic Surgery Affiliated Hangzhou First People’s Hospital Zhejiang University School of Medicine Hangzhou, Zhejiang, 310006, China
- Zhejiang University School of Medicine, Hangzhou, China
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Hangzhou, 310006, China
| | - Zhengyang Lu
- Department of Hepatobiliary and Pancreatic Surgery Affiliated Hangzhou First People’s Hospital Zhejiang University School of Medicine Hangzhou, Zhejiang, 310006, China
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Hangzhou, 310006, China
- Zhejiang Chinese Medical University, Hangzhou, 310053, PR China
| | - Wenzhi Shu
- Department of Hepatobiliary and Pancreatic Surgery Affiliated Hangzhou First People’s Hospital Zhejiang University School of Medicine Hangzhou, Zhejiang, 310006, China
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Hangzhou, 310006, China
| | - Ze Xiang
- Zhejiang University School of Medicine, Hangzhou, China
| | - Zhengxin Wang
- Department of General Surgery, Huashan Hospital, Fudan University Shanghai, 200040, China
| | - Xuyong Wei
- Department of Hepatobiliary and Pancreatic Surgery Affiliated Hangzhou First People’s Hospital Zhejiang University School of Medicine Hangzhou, Zhejiang, 310006, China
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Hangzhou, 310006, China
| | - Xiao Xu
- Zhejiang University School of Medicine, Hangzhou, China
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Hangzhou, 310006, China
- Institute of Organ Transplantation, Zhejiang University, Hangzhou, 310003, China
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4
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Xie Y, Yao J, Jin W, Ren L, Li X. Induction and Maturation of Hepatocyte-Like Cells In Vitro: Focus on Technological Advances and Challenges. Front Cell Dev Biol 2021; 9:765980. [PMID: 34901010 PMCID: PMC8662991 DOI: 10.3389/fcell.2021.765980] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2021] [Accepted: 11/08/2021] [Indexed: 12/17/2022] Open
Abstract
Limited by the poor proliferation and restricted sources of adult hepatocytes, there is an urgent need to find substitutes for proliferation and cultivation of mature hepatocytes in vitro for use in disease treatment, drug approval, and toxicity testing. Hepatocyte-like cells (HLCs), which originate from undifferentiated stem cells or modified adult cells, are considered good candidates because of their advantages in terms of cell source and in vitro expansion ability. However, the majority of induced HLCs are in an immature state, and their degree of differentiation is heterogeneous, diminishing their usability in basic research and limiting their clinical application. Therefore, various methods have been developed to promote the maturation of HLCs, including chemical approaches, alteration of cell culture systems, and genetic manipulation, to meet the needs of in vivo transplantation and in vitro model establishment. This review proposes different cell types for the induction of HLCs, and provide a comprehensive overview of various techniques to promote the generation and maturation of HLCs in vitro.
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Affiliation(s)
- Ye Xie
- The First Clinical Medical College, Lanzhou University, Lanzhou, China
| | - Jia Yao
- The First Clinical Medical College, Lanzhou University, Lanzhou, China.,Key Laboratory of Biotherapy and Regenerative Medicine of Gansu Province, Lanzhou, China
| | - Weilin Jin
- The First Clinical Medical College, Lanzhou University, Lanzhou, China.,Institute of Cancer Neuroscience, The First Hospital of Lanzhou University, Lanzhou, China.,The Medical Frontier Innovation Research Center, The First Hospital of Lanzhou University, Lanzhou, China
| | - Longfei Ren
- The First Clinical Medical College, Lanzhou University, Lanzhou, China.,The Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, China
| | - Xun Li
- The First Clinical Medical College, Lanzhou University, Lanzhou, China.,Key Laboratory of Biotherapy and Regenerative Medicine of Gansu Province, Lanzhou, China.,The Medical Frontier Innovation Research Center, The First Hospital of Lanzhou University, Lanzhou, China.,The Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, China.,Hepatopancreatobiliary Surgery Institute of Gansu Province, Lanzhou, China
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Xu Q. Human Three-Dimensional Hepatic Models: Cell Type Variety and Corresponding Applications. Front Bioeng Biotechnol 2021; 9:730008. [PMID: 34631680 PMCID: PMC8497968 DOI: 10.3389/fbioe.2021.730008] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2021] [Accepted: 08/30/2021] [Indexed: 12/23/2022] Open
Abstract
Owing to retained hepatic phenotypes and functions, human three-dimensional (3D) hepatic models established with diverse hepatic cell types are thought to recoup the gaps in drug development and disease modeling limited by a conventional two-dimensional (2D) cell culture system and species-specific variability in drug metabolizing enzymes and transporters. Primary human hepatocytes, human hepatic cancer cell lines, and human stem cell-derived hepatocyte-like cells are three main hepatic cell types used in current models and exhibit divergent hepatic phenotypes. Primary human hepatocytes derived from healthy hepatic parenchyma resemble in vivo-like genetic and metabolic profiling. Human hepatic cancer cell lines are unlimitedly reproducible and tumorigenic. Stem cell-derived hepatocyte-like cells derived from patients are promising to retain the donor's genetic background. It has been suggested in some studies that unique properties of cell types endue them with benefits in different research fields of in vitro 3D modeling paradigm. For instance, the primary human hepatocyte was thought to be the gold standard for hepatotoxicity study, and stem cell-derived hepatocyte-like cells have taken a main role in personalized medicine and regenerative medicine. However, the comprehensive review focuses on the hepatic cell type variety, and corresponding applications in 3D models are sparse. Therefore, this review summarizes the characteristics of different cell types and discusses opportunities of different cell types in drug development, liver disease modeling, and liver transplantation.
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Affiliation(s)
- Qianqian Xu
- School of Chinese Medicine, and Centre for Cancer and Inflammation Research, Hong Kong Baptist University, Hong Kong, China
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6
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Cox CR, Lynch S, Goldring C, Sharma P. Current Perspective: 3D Spheroid Models Utilizing Human-Based Cells for Investigating Metabolism-Dependent Drug-Induced Liver Injury. FRONTIERS IN MEDICAL TECHNOLOGY 2020; 2:611913. [PMID: 35047893 PMCID: PMC8757888 DOI: 10.3389/fmedt.2020.611913] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2020] [Accepted: 11/04/2020] [Indexed: 12/21/2022] Open
Abstract
Drug-induced liver injury (DILI) remains a leading cause for the withdrawal of approved drugs. This has significant financial implications for pharmaceutical companies, places increasing strain on global health services, and causes harm to patients. For these reasons, it is essential that in-vitro liver models are capable of detecting DILI-positive compounds and their underlying mechanisms, prior to their approval and administration to patients or volunteers in clinical trials. Metabolism-dependent DILI is an important mechanism of drug-induced toxicity, which often involves the CYP450 family of enzymes, and is associated with the production of a chemically reactive metabolite and/or inefficient removal and accumulation of potentially toxic compounds. Unfortunately, many of the traditional in-vitro liver models fall short of their in-vivo counterparts, failing to recapitulate the mature hepatocyte phenotype, becoming metabolically incompetent, and lacking the longevity to investigate and detect metabolism-dependent DILI and those associated with chronic and repeat dosing regimens. Nevertheless, evidence is gathering to indicate that growing cells in 3D formats can increase the complexity of these models, promoting a more mature-hepatocyte phenotype and increasing their longevity, in vitro. This review will discuss the use of 3D in vitro models, namely spheroids, organoids, and perfusion-based systems to establish suitable liver models to investigate metabolism-dependent DILI.
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Affiliation(s)
- Christopher R. Cox
- Department of Pharmacology and Experimental Therapeutics, MRC Centre for Drug Safety Science, Institute of Systems, Molecular & Integrative Biology, University of Liverpool, Liverpool, United Kingdom
- Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, United Kingdom
- *Correspondence: Christopher R. Cox
| | - Stephen Lynch
- Department of Pharmacology and Experimental Therapeutics, MRC Centre for Drug Safety Science, Institute of Systems, Molecular & Integrative Biology, University of Liverpool, Liverpool, United Kingdom
| | - Christopher Goldring
- Department of Pharmacology and Experimental Therapeutics, MRC Centre for Drug Safety Science, Institute of Systems, Molecular & Integrative Biology, University of Liverpool, Liverpool, United Kingdom
| | - Parveen Sharma
- Department of Pharmacology and Experimental Therapeutics, MRC Centre for Drug Safety Science, Institute of Systems, Molecular & Integrative Biology, University of Liverpool, Liverpool, United Kingdom
- Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, United Kingdom
- Liverpool Centre for Cardiovascular Science, Liverpool, United Kingdom
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Insulin/Glucose-Responsive Cells Derived from Induced Pluripotent Stem Cells: Disease Modeling and Treatment of Diabetes. Cells 2020; 9:cells9112465. [PMID: 33198288 PMCID: PMC7696367 DOI: 10.3390/cells9112465] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2020] [Revised: 11/03/2020] [Accepted: 11/09/2020] [Indexed: 12/21/2022] Open
Abstract
Type 2 diabetes, characterized by dysfunction of pancreatic β-cells and insulin resistance in peripheral organs, accounts for more than 90% of all diabetes. Despite current developments of new drugs and strategies to prevent/treat diabetes, there is no ideal therapy targeting all aspects of the disease. Restoration, however, of insulin-producing β-cells, as well as insulin-responsive cells, would be a logical strategy for the treatment of diabetes. In recent years, generation of transplantable cells derived from stem cells in vitro has emerged as an important research area. Pluripotent stem cells, either embryonic or induced, are alternative and feasible sources of insulin-secreting and glucose-responsive cells. This notwithstanding, consistent generation of robust glucose/insulin-responsive cells remains challenging. In this review, we describe basic concepts of the generation of induced pluripotent stem cells and subsequent differentiation of these into pancreatic β-like cells, myotubes, as well as adipocyte- and hepatocyte-like cells. Use of these for modeling of human disease is now feasible, while development of replacement therapies requires continued efforts.
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Abstract
The organoid model represents a major breakthrough in cell biology that has revolutionised biomedical research. Organoids are 3D physiological in vitro structures that recapitulate morphological and functional features of in vivo tissues and offer significant advantages over traditional cell culture methods. Liver organoids are of particular interest because of the pleiotropy of functions exerted by the human liver, their utility to model different liver diseases, and their potential application as cell-based therapies in regenerative medicine. Moreover, because they can be derived from patient tissues, organoid models offer new perspectives in personalised medicine and drug discovery. In this review, we discuss the current liver organoid models for the study of liver disease.
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Key Words
- 3D cultures
- A1AT, alpha-1 antitrypsin
- ALD, alcohol-related liver disease
- CCA, cholangiocarcinoma
- CFTR, cystic fibrosis transmembrane conductance regulator
- CHC, combined hepato-cholangiocarcinoma
- CLD, chronic liver disease
- CTLN1, citrullinemia type 1
- Chol-orgs, cholangiocyte organoids
- Disease modelling
- EGF, epidermal growth factor
- ER, endoplasmic reticulum
- ESCs, embryonic stem cells
- FFAs, free fatty acids
- HCC, hepatocellular carcinoma
- HUVEC, human umbilical vein endothelial cells
- Hep-orgs, hepatocyte organoids
- IL-, interleukin-
- Liver disease
- MSC, mesenchymal stem cell
- NAFLD, non-alcoholic fatty liver disease
- Organoids
- PDO, patient-derived organoid
- PDX, patient-derived xenograft
- PHH, primary human hepatocyte
- PSC, primary sclerosing cholangitis
- Personalised medicine
- Preclinical models
- iPSC, induced pluripotent stem cell
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Affiliation(s)
- Sandro Nuciforo
- Department of Biomedicine, University Hospital Basel, University of Basel, CH-4031 Basel, Switzerland
| | - Markus H Heim
- Department of Biomedicine, University Hospital Basel, University of Basel, CH-4031 Basel, Switzerland.,Clarunis, University Center for Gastrointestinal and Liver Diseases, CH-4002 Basel, Switzerland
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Fang M, Liu LP, Zhou H, Li YM, Zheng YW. Practical choice for robust and efficient differentiation of human pluripotent stem cells. World J Stem Cells 2020; 12:752-760. [PMID: 32952856 PMCID: PMC7477655 DOI: 10.4252/wjsc.v12.i8.752] [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: 03/28/2020] [Revised: 04/30/2020] [Accepted: 07/01/2020] [Indexed: 02/06/2023] Open
Abstract
Human pluripotent stem cells (hPSCs) have the distinct advantage of being able to differentiate into cells of all three germ layers. Target cells or tissues derived from hPSCs have many uses such as drug screening, disease modeling, and transplantation therapy. There are currently a wide variety of differentiation methods available. However, most of the existing differentiation methods are unreliable, with uneven differentiation efficiency and poor reproducibility. At the same time, it is difficult to choose the optimal method when faced with so many differentiation schemes, and it is time-consuming and costly to explore a new differentiation approach. Thus, it is critical to design a robust and efficient method of differentiation. In this review article, we summarize a comprehensive approach in which hPSCs are differentiated into target cells or organoids including brain, liver, blood, melanocytes, and mesenchymal cells. This was accomplished by employing an embryoid body-based three-dimensional (3D) suspension culture system with multiple cells co-cultured. The method has high stable differentiation efficiency compared to the conventional 2D culture and can meet the requirements of clinical application. Additionally, ex vivo co-culture models might be able to constitute organoids that are highly similar or mimic human organs for potential organ transplantation in the future.
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Affiliation(s)
- Mei Fang
- Institute of Regenerative Medicine, Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang 212001, Jiangsu Province, China
| | - Li-Ping Liu
- Institute of Regenerative Medicine, Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang 212001, Jiangsu Province, China
| | - Hang Zhou
- Institute of Regenerative Medicine, Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang 212001, Jiangsu Province, China
| | - Yu-Mei Li
- Institute of Regenerative Medicine, Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang 212001, Jiangsu Province, China
| | - Yun-Wen Zheng
- Institute of Regenerative Medicine, Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang 212001, Jiangsu Province, China
- School of Biotechnology and Heath Sciences, Wuyi University, Jiangmen 529020, Guangdong Province, China
- Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, University of Tsukuba Faculty of Medicine, Tsukuba, Ibaraki 305-8575, Japan
- Yokohama City University School of Medicine, Yokohama, Kanagawa 234-0006, Japan
- Division of Regenerative Medicine, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, the University of Tokyo, Tokyo 108-8639, Japan.
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Cernigliaro V, Peluso R, Zedda B, Silengo L, Tolosano E, Pellicano R, Altruda F, Fagoonee S. Evolving Cell-Based and Cell-Free Clinical Strategies for Treating Severe Human Liver Diseases. Cells 2020; 9:386. [PMID: 32046114 PMCID: PMC7072646 DOI: 10.3390/cells9020386] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2019] [Revised: 01/21/2020] [Accepted: 02/06/2020] [Indexed: 02/07/2023] Open
Abstract
Liver diseases represent a major global health issue, and currently, liver transplantation is the only viable alternative to reduce mortality rates in patients with end-stage liver diseases. However, scarcity of donor organs and risk of recidivism requiring a re-transplantation remain major obstacles. Hence, much hope has turned towards cell-based therapy. Hepatocyte-like cells obtained from embryonic stem cells or adult stem cells bearing multipotent or pluripotent characteristics, as well as cell-based systems, such as organoids, bio-artificial liver devices, bioscaffolds and organ printing are indeed promising. New approaches based on extracellular vesicles are also being investigated as cell substitutes. Extracellular vesicles, through the transfer of bioactive molecules, can modulate liver regeneration and restore hepatic function. This review provides an update on the current state-of-art cell-based and cell-free strategies as alternatives to liver transplantation for patients with end-stage liver diseases.
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Affiliation(s)
- Viviana Cernigliaro
- Department of Molecular Biotechnology and Health Sciences, University of Turin, Via Nizza 52, 10126 Turin, Italy; (V.C.); (R.P.); (B.Z.)
- Maria Pia Hospital, 10126 Turin, Italy
| | - Rossella Peluso
- Department of Molecular Biotechnology and Health Sciences, University of Turin, Via Nizza 52, 10126 Turin, Italy; (V.C.); (R.P.); (B.Z.)
- Maria Pia Hospital, 10126 Turin, Italy
| | - Beatrice Zedda
- Department of Molecular Biotechnology and Health Sciences, University of Turin, Via Nizza 52, 10126 Turin, Italy; (V.C.); (R.P.); (B.Z.)
- Maria Pia Hospital, 10126 Turin, Italy
| | - Lorenzo Silengo
- Molecular Biotechnology Center, Departmet of Molecular Biotechnology and Health Sciences, University of Turin, Via Nizza 52, 10126 Turin, Italy; (L.S.); (E.T.)
| | - Emanuela Tolosano
- Molecular Biotechnology Center, Departmet of Molecular Biotechnology and Health Sciences, University of Turin, Via Nizza 52, 10126 Turin, Italy; (L.S.); (E.T.)
| | | | - Fiorella Altruda
- Molecular Biotechnology Center, Departmet of Molecular Biotechnology and Health Sciences, University of Turin, Via Nizza 52, 10126 Turin, Italy; (L.S.); (E.T.)
| | - Sharmila Fagoonee
- Institute of Biostructure and Bioimaging, National Research Council, Molecular Biotechnology Center, Via Nizza 52, 10126 Turin, Italy
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