|
1
|
Torabinavid P, Khosropanah MH, Azimzadeh A, Kajbafzadeh AM. Current strategies on kidney regeneration using tissue engineering approaches: a systematic review. BMC Nephrol 2025; 26:66. [PMID: 39934739 PMCID: PMC11816546 DOI: 10.1186/s12882-025-03968-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2024] [Accepted: 01/17/2025] [Indexed: 02/13/2025] Open
Abstract
INTRODUCTION Over the past two decades, there has been a notable rise in the number of individuals afflicted with End-Stage Renal Disease, resulting in an increased demand for renal replacement therapies. While periodic dialysis is beneficial, it can negatively impact a patient's quality of life and does not fully replicate the secretory functions of the kidneys. Additionally, the scarcity of organ donors and complications associated with organ transplants have underscored the importance of tissue engineering. Regenerative medicine is revolutionized by developing decellularized organs and tissue engineering, which is considered a cutting-edge area of study with enormous potential. Developing bioengineered kidneys using tissue engineering approaches for renal replacement therapy is promising. METHOD AND MATERIALS We aimed to systematically review the essential preclinical data to promote the translation of tissue engineering research for kidney repair from the laboratory to clinical practice. A PubMed search strategy was systematically implemented without any linguistic restrictions. The assessment focused on complete circumferential and inlay procedures, thoroughly evaluating parameters such as cell seeding, decellularization techniques, recellularization protocols, and biomaterial types. RESULTS Of the 1,484 studies retrieved from the following primary searches, 105 were included. Kidneys were harvested from eight different species. Nine studies performed kidney decellularization from discarded human kidneys. Sixty-four studies performed whole organ decellularization. Some studies used acellular scaffolds to produce hydrogels, sheets, and solutions. Decellularization is achieved through physical, chemical, or enzymatic treatment or a combination of them. Sterilization of acellular scaffolds was also thoroughly and comparatively evaluated. Lastly, different recellularization protocols and types of cells used for further cell seeding were demonstrated. CONCLUSION A comprehensive review of the existing literature about kidney tissue engineering was conducted to evaluate its effectiveness in preclinical investigations. Our findings indicate that enhancements in the design of preclinical studies are necessary to facilitate the successful translation of tissue engineering technologies into clinical applications.
Collapse
Affiliation(s)
- Parham Torabinavid
- Pediatric Urology and Regenerative Medicine Research Center, Gene, Cell and Tissue Research Institute, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Hossein Khosropanah
- Pediatric Urology and Regenerative Medicine Research Center, Gene, Cell and Tissue Research Institute, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Ashkan Azimzadeh
- Pediatric Urology and Regenerative Medicine Research Center, Gene, Cell and Tissue Research Institute, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Abdol-Mohammad Kajbafzadeh
- Pediatric Urology and Regenerative Medicine Research Center, Gene, Cell and Tissue Research Institute, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.
- Pediatric Urology and Regenerative Medicine Research Center, Pediatric Center of Excellence, Children's Medical Center, No. 62, Dr. Qarib's St, Keshavarz Blvd, Tehran, 14194 33151, Iran.
| |
Collapse
|
|
2
|
Hussein KH, Ahmadzada B, Correa JC, Sultan A, Wilken S, Amiot B, Nyberg SL. Liver tissue engineering using decellularized scaffolds: Current progress, challenges, and opportunities. Bioact Mater 2024; 40:280-305. [PMID: 38973992 PMCID: PMC11226731 DOI: 10.1016/j.bioactmat.2024.06.001] [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: 04/03/2024] [Revised: 05/30/2024] [Accepted: 06/01/2024] [Indexed: 07/09/2024] Open
Abstract
Liver transplantation represents the only definitive treatment for patients with end-stage liver disease. However, the shortage of liver donors provokes a dramatic gap between available grafts and patients on the waiting list. Whole liver bioengineering, an emerging field of tissue engineering, holds great potential to overcome this gap. This approach involves two main steps; the first is liver decellularization and the second is recellularization. Liver decellularization aims to remove cellular and nuclear materials from the organ, leaving behind extracellular matrices containing different structural proteins and growth factors while retaining both the vascular and biliary networks. Recellularization involves repopulating the decellularized liver with appropriate cells, theoretically from the recipient patient, to reconstruct the parenchyma, vascular tree, and biliary network. The aim of this review is to identify the major advances in decellularization and recellularization strategies and investigate obstacles for the clinical application of bioengineered liver, including immunogenicity of the designed liver extracellular matrices, the need for standardization of scaffold fabrication techniques, selection of suitable cell sources for parenchymal repopulation, vascular, and biliary tree reconstruction. In vivo transplantation models are also summarized for evaluating the functionality of bioengineered livers. Finally, the regulatory measures and future directions for confirming the safety and efficacy of bioengineered liver are also discussed. Addressing these challenges in whole liver bioengineering may offer new solutions to meet the demand for liver transplantation and improve patient outcomes.
Collapse
Affiliation(s)
- Kamal H. Hussein
- Department of Surgery, Mayo Clinic, Rochester, MN, United States
- William J. von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, MN, United States
- Department of Surgery, Anesthesiology, and Radiology, College of Veterinary Medicine, Assiut University, Assiut, Egypt
| | - Boyukkhanim Ahmadzada
- Department of Surgery, Mayo Clinic, Rochester, MN, United States
- William J. von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, MN, United States
| | - Julio Cisneros Correa
- Department of Surgery, Mayo Clinic, Rochester, MN, United States
- William J. von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, MN, United States
| | - Ahmer Sultan
- Department of Surgery, Mayo Clinic, Rochester, MN, United States
- William J. von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, MN, United States
| | - Silvana Wilken
- Department of Surgery, Mayo Clinic, Rochester, MN, United States
- William J. von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, MN, United States
| | - Bruce Amiot
- Department of Surgery, Mayo Clinic, Rochester, MN, United States
- William J. von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, MN, United States
| | - Scott L. Nyberg
- Department of Surgery, Mayo Clinic, Rochester, MN, United States
- William J. von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, MN, United States
| |
Collapse
|
|
3
|
García-Gareta E, Calderón-Villalba A, Alamán-Díez P, Costa CG, Guerrero PE, Mur C, Flores AR, Jurjo NO, Sancho P, Pérez MÁ, García-Aznar JM. Physico-chemical characterization of the tumour microenvironment of pancreatic ductal adenocarcinoma. Eur J Cell Biol 2024; 103:151396. [PMID: 38359522 DOI: 10.1016/j.ejcb.2024.151396] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2023] [Revised: 01/25/2024] [Accepted: 02/10/2024] [Indexed: 02/17/2024] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive lethal malignancy that accounts for more than 90% of pancreatic cancer diagnoses. Our research is focused on the physico-chemical properties of the tumour microenvironment (TME), including its tumoural extracellular matrix (tECM), as they may have an important impact on the success of cancer therapies. PDAC xenografts and their decellularized tECM offer a great material source for research in terms of biomimicry with the original human tumour. Our aim was to evaluate and quantify the physico-chemical properties of the PDAC TME. Both cellularized (native TME) and decellularized (tECM) patient-derived PDAC xenografts were analyzed. A factorial design of experiments identified an optimal combination of factors for effective xenograft decellularization. Our results provide a complete advance in our understanding of the PDAC TME and its corresponding stroma, showing that it presents an interconnected porous architecture with very low permeability and small pores due to the contractility of the cellular components. This fact provides a potential therapeutic strategy based on the therapeutic agent size.
Collapse
Affiliation(s)
- Elena García-Gareta
- Multiscale in Mechanical & Biological Engineering Research Group, Aragon Institute of Engineering Research (I3A), School of Engineering & Architecture, University of Zaragoza, Zaragoza, Aragon, Spain; Aragon Institute for Health Research (IIS Aragon), Miguel Servet University Hospital, Zaragoza, Aragon, Spain; Division of Biomaterials & Tissue Engineering, UCL Eastman Dental Institute, University College London, London, United Kingdom.
| | - Alejandro Calderón-Villalba
- Multiscale in Mechanical & Biological Engineering Research Group, Aragon Institute of Engineering Research (I3A), School of Engineering & Architecture, University of Zaragoza, Zaragoza, Aragon, Spain
| | - Pilar Alamán-Díez
- Multiscale in Mechanical & Biological Engineering Research Group, Aragon Institute of Engineering Research (I3A), School of Engineering & Architecture, University of Zaragoza, Zaragoza, Aragon, Spain
| | - Carlos Gracia Costa
- Multiscale in Mechanical & Biological Engineering Research Group, Aragon Institute of Engineering Research (I3A), School of Engineering & Architecture, University of Zaragoza, Zaragoza, Aragon, Spain
| | - Pedro Enrique Guerrero
- Multiscale in Mechanical & Biological Engineering Research Group, Aragon Institute of Engineering Research (I3A), School of Engineering & Architecture, University of Zaragoza, Zaragoza, Aragon, Spain
| | - Carlota Mur
- Aragon Institute of Engineering Research (I3A), School of Engineering & Architecture, University of Zaragoza, Zaragoza, Aragon, Spain
| | - Ana Rueda Flores
- Multiscale in Mechanical & Biological Engineering Research Group, Aragon Institute of Engineering Research (I3A), School of Engineering & Architecture, University of Zaragoza, Zaragoza, Aragon, Spain
| | - Nerea Olivera Jurjo
- Multiscale in Mechanical & Biological Engineering Research Group, Aragon Institute of Engineering Research (I3A), School of Engineering & Architecture, University of Zaragoza, Zaragoza, Aragon, Spain
| | - Patricia Sancho
- Aragon Institute for Health Research (IIS Aragon), Miguel Servet University Hospital, Zaragoza, Aragon, Spain
| | - María Ángeles Pérez
- Multiscale in Mechanical & Biological Engineering Research Group, Aragon Institute of Engineering Research (I3A), School of Engineering & Architecture, University of Zaragoza, Zaragoza, Aragon, Spain; Aragon Institute for Health Research (IIS Aragon), Miguel Servet University Hospital, Zaragoza, Aragon, Spain
| | - José Manuel García-Aznar
- Multiscale in Mechanical & Biological Engineering Research Group, Aragon Institute of Engineering Research (I3A), School of Engineering & Architecture, University of Zaragoza, Zaragoza, Aragon, Spain; Aragon Institute for Health Research (IIS Aragon), Miguel Servet University Hospital, Zaragoza, Aragon, Spain
| |
Collapse
|
|
4
|
Nishimura Y. Current status and future prospects of decellularized kidney tissue. J Artif Organs 2023; 26:171-175. [PMID: 36138180 DOI: 10.1007/s10047-022-01366-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2022] [Accepted: 09/12/2022] [Indexed: 11/29/2022]
Abstract
End-stage renal disease (ESRD) is characterized by progressive loss of kidney function, which can result in damage to various tissues and organs. Dialysis therapy and kidney transplantation are currently the only therapeutic options available for patients with ESRD. In the case of kidney transplantation, organ shortage and high organ rejection have increased the need for novel treatment modalities. Therefore, organ regeneration employing decellularization technology has emerged as a viable alternative to conventional organ transplantation. In this technology, organs are decellularized using physical, chemical, or biological means to create a natural scaffold and foundation for cell seeding. After in vivo transplantation, this scaffold can be recellularized using stem cells or adult differentiated cells, resulting in a functional organ devoid of immune response. This review focuses on the primary agents used for renal decellularization and the current status of kidney regeneration using decellularization.
Collapse
Affiliation(s)
- Yusuke Nishimura
- Course of Clinical Engineering, Kitasato Junior College of Health Hygienic Sciences, Minamiuonuma City, Niigata, 500 Kurotsuchishinden 949-7241, Japan.
| |
Collapse
|
|
5
|
Almeida GHDR, da Silva-Júnior LN, Gibin MS, Dos Santos H, de Oliveira Horvath-Pereira B, Pinho LBM, Baesso ML, Sato F, Hernandes L, Long CR, Relly L, Miglino MA, Carreira ACO. Perfusion and Ultrasonication Produce a Decellularized Porcine Whole-Ovary Scaffold with a Preserved Microarchitecture. Cells 2023; 12:1864. [PMID: 37508528 PMCID: PMC10378497 DOI: 10.3390/cells12141864] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2023] [Revised: 04/17/2023] [Accepted: 04/18/2023] [Indexed: 07/30/2023] Open
Abstract
The application of decellularized scaffolds for artificial tissue reconstruction has been an approach with great therapeutic potential in regenerative medicine. Recently, biomimetic ovarian tissue reconstruction was proposed to reestablish ovarian endocrine functions. Despite many decellularization methods proposed, there is no established protocol for whole ovaries by detergent perfusion that is able to preserve tissue macro and microstructure with higher efficiency. This generated biomaterial may have the potential to be applied for other purposes beyond reproduction and be translated to other areas in the tissue engineering field. Therefore, this study aimed to establish and standardize a protocol for porcine ovaries' decellularization based on detergent perfusion and ultrasonication to obtain functional whole-ovary scaffolds. For that, porcine ovaries (n = 5) were perfused with detergents (0.5% SDS and 1% Triton X-100) and submitted to an ultrasonication bath to produce acellular scaffolds. The decellularization efficiency was evaluated by DAPI staining and total genomic DNA quantification. ECM morphological evaluation was performed by histological, immunohistochemistry, and ultrastructural analyses. ECM physico-chemical composition was evaluated using FTIR and Raman spectroscopy. A cytocompatibility and cell adhesion assay using murine fibroblasts was performed. Results showed that the proposed method was able to remove cellular components efficiently. There was no significant ECM component loss in relation to native tissue, and the scaffolds were cytocompatible and allowed cell attachment. In conclusion, the proposed decellularization protocol produced whole-ovaries scaffolds with preserved ECM composition and great potential for application in tissue engineering.
Collapse
Affiliation(s)
| | | | | | - Henrique Dos Santos
- Department of Physics, State University of Maringá, Maringá 87020-900, Brazil
| | | | - Leticia Beatriz Mazo Pinho
- Department of Surgery, School of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo 05508-270, Brazil
| | | | - Francielle Sato
- Department of Physics, State University of Maringá, Maringá 87020-900, Brazil
| | - Luzmarina Hernandes
- Department of Morphological Sciences, State University of Maringa, Maringá 87020-900, Brazil
| | - Charles R Long
- Department of Veterinary Physiology and Pharmacology, School of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX 77843, USA
| | - Luciana Relly
- Department of Veterinary Physiology and Pharmacology, School of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX 77843, USA
| | - Maria Angelica Miglino
- Department of Surgery, School of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo 05508-270, Brazil
| | - Ana Claudia Oliveira Carreira
- Department of Surgery, School of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo 05508-270, Brazil
- Centre for Natural and Human Sciences, Federal University of ABC, Santo André, São Paulo 09210-580, Brazil
| |
Collapse
|
|
6
|
Afzal Z, Huguet EL. Bioengineering liver tissue by repopulation of decellularised scaffolds. World J Hepatol 2023; 15:151-179. [PMID: 36926238 PMCID: PMC10011915 DOI: 10.4254/wjh.v15.i2.151] [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: 10/26/2022] [Revised: 11/22/2022] [Accepted: 02/15/2023] [Indexed: 02/24/2023] Open
Abstract
Liver transplantation is the only curative therapy for end stage liver disease, but is limited by the organ shortage, and is associated with the adverse consequences of immunosuppression. Repopulation of decellularised whole organ scaffolds with appropriate cells of recipient origin offers a theoretically attractive solution, allowing reliable and timely organ sourcing without the need for immunosuppression. Decellularisation methodologies vary widely but seek to address the conflicting objectives of removing the cellular component of tissues whilst keeping the 3D structure of the extra-cellular matrix intact, as well as retaining the instructive cell fate determining biochemicals contained therein. Liver scaffold recellularisation has progressed from small rodent in vitro studies to large animal in vivo perfusion models, using a wide range of cell types including primary cells, cell lines, foetal stem cells, and induced pluripotent stem cells. Within these models, a limited but measurable degree of physiologically significant hepatocyte function has been reported with demonstrable ammonia metabolism in vivo. Biliary repopulation and function have been restricted by challenges relating to the culture and propagations of cholangiocytes, though advances in organoid culture may help address this. Hepatic vasculature repopulation has enabled sustainable blood perfusion in vivo, but with cell types that would limit clinical applications, and which have not been shown to have the specific functions of liver sinusoidal endothelial cells. Minority cell groups such as Kupffer cells and stellate cells have not been repopulated. Bioengineering by repopulation of decellularised scaffolds has significantly progressed, but there remain significant experimental challenges to be addressed before therapeutic applications may be envisaged.
Collapse
Affiliation(s)
- Zeeshan Afzal
- Department of Surgery, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre; Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| | - Emmanuel Laurent Huguet
- Department of Surgery, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre; Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| |
Collapse
|
|
7
|
Salti H, Kramer L, Nelz SC, Lorenz M, Breitrück A, Hofrichter J, Frank M, Schulz K, Mitzner S, Wasserkort R. Decellularization of precision-cut kidney slices-application of physical and chemical methods. Biomed Mater 2023; 18:025004. [PMID: 36599165 DOI: 10.1088/1748-605x/acb02e] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2022] [Accepted: 01/04/2023] [Indexed: 01/05/2023]
Abstract
The extracellular matrix (ECM) obtained by decellularization provides scaffolds with the natural complex architecture and biochemical composition of the target organ. Whole kidney decellularization by perfusion uses the vasculature to remove cells leaving a scaffold that can be recellularized with patient-specific cells. However, decellularization and recellularization are highly complex processes that require intensive optimization of various parameters. In pursuit of this, a huge number of animals must be sacrificed. Therefore, we used precision-cut kidney slices (PCKS) as a source of natural scaffolds, which were decellularized by immersion in chemical reagents allowing the examination of more parameters with less animals. However, chemical reagents have a damaging effect on the structure and components of the ECM. Therefore, this study aimed at investigating the effects of physical treatment methods on the effectiveness of PCKS decellularization by immersion in chemical reagents (CHEM). PCKS were treated physically before or during immersion in chemicals (CHEM) with high hydrostatic pressure (HHP), freezing-thawing cycles (FTC) or in an ultrasonic bath system (UBS). Biochemical and DNA quantification as well as structural evaluation with conventional histology and scanning electron microscopy (SEM) were performed. Compared to decellularization by CHEM alone, FTC treatment prior to CHEM was the most effective in reducing DNA while also preserving glycosaminoglycan (GAG) content. Moreover, while UBS resulted in a comparable reduction of DNA, it was the least effective in retaining GAGs. In contrast, despite the pretreatment with HHP with pressures up to 200 MPa, it was the least effective in DNA removal. Histological scoring showed that HHP scaffolds received the best score followed by UBS, FTC and CHEM scaffolds. However further analysis with SEM demonstrated a higher deterioration of the ultrastructure in UBS scaffolds. Altogether, pretreatment with FTC prior to CHEM resulted in a better balance between DNA removal and structural preservation.
Collapse
Affiliation(s)
- Haitham Salti
- Department of Extracorporeal Therapy Systems (EXTHER), Fraunhofer Institute for Cell Therapy and Immunology (IZI), Rostock, Germany
| | - Lea Kramer
- Department of Extracorporeal Therapy Systems (EXTHER), Fraunhofer Institute for Cell Therapy and Immunology (IZI), Rostock, Germany
| | - Sophie-Charlotte Nelz
- Department of Extracorporeal Therapy Systems (EXTHER), Fraunhofer Institute for Cell Therapy and Immunology (IZI), Rostock, Germany
- Division of Nephrology, Department of Internal Medicine, Rostock University Medical Center, Rostock, Germany
| | - Mathias Lorenz
- Wismar University of Applied Sciences, Faculty of Engineering, Wismar, Germany
| | - Anne Breitrück
- Department of Extracorporeal Therapy Systems (EXTHER), Fraunhofer Institute for Cell Therapy and Immunology (IZI), Rostock, Germany
- Division of Nephrology, Department of Internal Medicine, Rostock University Medical Center, Rostock, Germany
| | - Jacqueline Hofrichter
- Department of Extracorporeal Therapy Systems (EXTHER), Fraunhofer Institute for Cell Therapy and Immunology (IZI), Rostock, Germany
- Division of Nephrology, Department of Internal Medicine, Rostock University Medical Center, Rostock, Germany
| | - Marcus Frank
- Medical Biology and Electron Microscopy Centre, Rostock University Medical Center, Rostock, Germany
- Department Life Light & Matter, University of Rostock, Rostock, Germany
| | - Karoline Schulz
- Medical Biology and Electron Microscopy Centre, Rostock University Medical Center, Rostock, Germany
| | - Steffen Mitzner
- Department of Extracorporeal Therapy Systems (EXTHER), Fraunhofer Institute for Cell Therapy and Immunology (IZI), Rostock, Germany
- Division of Nephrology, Department of Internal Medicine, Rostock University Medical Center, Rostock, Germany
| | - Reinhold Wasserkort
- Department of Extracorporeal Therapy Systems (EXTHER), Fraunhofer Institute for Cell Therapy and Immunology (IZI), Rostock, Germany
- Division of Nephrology, Department of Internal Medicine, Rostock University Medical Center, Rostock, Germany
| |
Collapse
|
|
8
|
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.
Collapse
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,
| |
Collapse
|
|
9
|
Moffat D, Ye K, Jin S. Decellularization for the retention of tissue niches. J Tissue Eng 2022; 13:20417314221101151. [PMID: 35620656 PMCID: PMC9128068 DOI: 10.1177/20417314221101151] [Citation(s) in RCA: 62] [Impact Index Per Article: 20.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Accepted: 05/01/2022] [Indexed: 12/25/2022] Open
Abstract
Decellularization of natural tissues to produce extracellular matrix is a promising method for three-dimensional scaffolding and for understanding microenvironment of the tissue of interest. Due to the lack of a universal standard protocol for tissue decellularization, recent investigations seek to develop novel methods for whole or partial organ decellularization capable of supporting cell differentiation and implantation towards appropriate tissue regeneration. This review provides a comprehensive and updated perspective on the most recent advances in decellularization strategies for a variety of organs and tissues, highlighting techniques of chemical, physical, biological, enzymatic, or combinative-based methods to remove cellular contents from tissues. In addition, the review presents modernized approaches for improving standard decellularization protocols for numerous organ types.
Collapse
Affiliation(s)
- Deana Moffat
- Department of Biomedical Engineering, Binghamton University, State University of New York (SUNY), Binghamton, NY, USA
| | - Kaiming Ye
- Department of Biomedical Engineering, Binghamton University, State University of New York (SUNY), Binghamton, NY, USA
- Center of Biomanufacturing for Regenerative Medicine, Binghamton University, State University of New York (SUNY), Binghamton, NY, USA
| | - Sha Jin
- Department of Biomedical Engineering, Binghamton University, State University of New York (SUNY), Binghamton, NY, USA
- Center of Biomanufacturing for Regenerative Medicine, Binghamton University, State University of New York (SUNY), Binghamton, NY, USA
| |
Collapse
|
|
10
|
Have we hit a wall with whole kidney decellularization and recellularization: A review. CURRENT OPINION IN BIOMEDICAL ENGINEERING 2021. [DOI: 10.1016/j.cobme.2021.100335] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
|
|
11
|
Klak M, Łojszczyk I, Berman A, Tymicki G, Adamiok-Ostrowska A, Sierakowski M, Olkowski R, Szczepankiewicz AA, Kamiński A, Dobrzyń A, Wszoła M. Impact of Porcine Pancreas Decellularization Conditions on the Quality of Obtained dECM. Int J Mol Sci 2021; 22:ijms22137005. [PMID: 34209772 PMCID: PMC8267664 DOI: 10.3390/ijms22137005] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2021] [Revised: 06/20/2021] [Accepted: 06/23/2021] [Indexed: 12/14/2022] Open
Abstract
Due to the limited number of organ donors, 3D printing of organs is a promising technique. Tissue engineering is increasingly using xenogeneic material for this purpose. This study was aimed at assessing the safety of decellularized porcine pancreas, together with the analysis of the risk of an undesirable immune response. We tested eight variants of the decellularization process. We determined the following impacts: rinsing agents (PBS/NH3·H2O), temperature conditions (4 °C/24 °C), and the grinding method of native material (ground/cut). To assess the quality of the extracellular matrix after the completed decellularization process, analyses of the following were performed: DNA concentration, fat content, microscopic evaluation, proteolysis, material cytotoxicity, and most importantly, the Triton X-100 content. Our analyses showed that we obtained a product with an extremely low detergent content with negligible residual DNA content. The obtained results confirmed the performed histological and immuno-fluorescence staining. Moreover, the TEM microscopic analysis proved that the correct collagen structure was preserved after the decellularization process. Based on the obtained results, we chose the most favorable variant in terms of quality and biology. The method we chose is an effective and safe method that gives a chance for the development of transplant and regenerative medicine.
Collapse
Affiliation(s)
- Marta Klak
- Foundation of Research and Science Development, 01-793 Warsaw, Poland; (M.K.); (I.Ł.); (A.B.); (G.T.); (A.A.-O.)
- Polbionica Ltd., 01-793 Warsaw, Poland
| | - Ilona Łojszczyk
- Foundation of Research and Science Development, 01-793 Warsaw, Poland; (M.K.); (I.Ł.); (A.B.); (G.T.); (A.A.-O.)
| | - Andrzej Berman
- Foundation of Research and Science Development, 01-793 Warsaw, Poland; (M.K.); (I.Ł.); (A.B.); (G.T.); (A.A.-O.)
- Polbionica Ltd., 01-793 Warsaw, Poland
- Medispace Medical Centre, 01-044 Warsaw, Poland
| | - Grzegorz Tymicki
- Foundation of Research and Science Development, 01-793 Warsaw, Poland; (M.K.); (I.Ł.); (A.B.); (G.T.); (A.A.-O.)
| | - Anna Adamiok-Ostrowska
- Foundation of Research and Science Development, 01-793 Warsaw, Poland; (M.K.); (I.Ł.); (A.B.); (G.T.); (A.A.-O.)
- Department of Biochemistry and Molecular Biology, Centre of Postgraduate Medical Education, 01-813 Warsaw, Poland
| | - Maciej Sierakowski
- Institute of Biological Sciences, Cardinal Stefan Wyszynski University in Warsaw, Wóycickiego 1/3, 01-938 Warsaw, Poland;
| | - Radosław Olkowski
- Department of Transplantology and Central Tissue Bank, Medical University of Warsaw, 02-004 Warsaw, Poland; (R.O.); (A.K.)
| | - Andrzej Antoni Szczepankiewicz
- Laboratory of Electron Microscopy, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteur Street, 02-093 Warsaw, Poland;
| | - Artur Kamiński
- Department of Transplantology and Central Tissue Bank, Medical University of Warsaw, 02-004 Warsaw, Poland; (R.O.); (A.K.)
| | | | - Michał Wszoła
- Foundation of Research and Science Development, 01-793 Warsaw, Poland; (M.K.); (I.Ł.); (A.B.); (G.T.); (A.A.-O.)
- Polbionica Ltd., 01-793 Warsaw, Poland
- Medispace Medical Centre, 01-044 Warsaw, Poland
- Correspondence:
| |
Collapse
|
|
12
|
Rabbani M, Zakian N, Alimoradi N. Contribution of Physical Methods in Decellularization of Animal Tissues. JOURNAL OF MEDICAL SIGNALS & SENSORS 2021; 11:1-11. [PMID: 34026585 PMCID: PMC8043117 DOI: 10.4103/jmss.jmss_2_20] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2020] [Revised: 02/19/2020] [Accepted: 07/19/2020] [Indexed: 01/12/2023]
Abstract
Biologic scaffolds composed of extracellular matrix (ECM) are frequently used for clinical purposes of tissue regeneration. Different methods have been developed for this purpose. All methods of decellularization including chemical and physical approaches leave some damage on the ECM; however, the effects of these methods are different which make some of these procedures more proper to maintain ECM structure than other methods. This review is aimed to introduce and compare new physical methods for the decellularization of different tissues and organs in tissue engineering. All recent reports and research that have used at least one physical method in the procedure of decellularization, were included and evaluated in this paper. The advantages and drawbacks of each method were examined and compared considering the effectiveness. This review tried to highlight the prospective potentials and benefits of applying physical methods for decellularization protocols in tissue engineering instead of the current chemical methods. These chemical methods are harsh in nature and were shown to be destructive and harmful to essential substances of ECM and scaffold structure. Therefore, using physical methods as a partial or even a whole protocol could save time, costs, and quality of the final acellular tissue in complicated decellularization procedures. Moreover, regarding the control factor that could be achieved easily with physical methods, optimization of different decellularization protocols would be quite satisfactory. Combined methods take advantage of both chemical and physical approaches.
Collapse
Affiliation(s)
- Mohsen Rabbani
- Department of Biomedical Engineering, University of Isfahan, Isfahan, Iran
| | - Nasrin Zakian
- Department of Biomedical Engineering, University of Isfahan, Isfahan, Iran
| | - Nima Alimoradi
- Department of Biomedical Engineering, University of Isfahan, Isfahan, Iran
| |
Collapse
|
|
13
|
Sokol A, Grekov D, Yemets G, Galkin A, Shchotkina N, Dovghaliuk A, Rudenko N, Yemets I. The Efficiency of Decellularization of Bovine Pericardium by Different Concentrations of Sodium Dodecyl Sulfate. INNOVATIVE BIOSYSTEMS AND BIOENGINEERING 2020. [DOI: 10.20535/ibb.2020.4.4.214765] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
|