Procedure for Decellularization of Rat Livers in an Oscillating-pressure Perfusion Device

Hillebrandt, Karl H.; Polenz, Dietrich; Butter, Antje; Tang, Peter; Reutzel‐Selke, Anja; Ανδρέου, Ανδρέας; Napierala, Hendrik; Raschzok, Nathanael; Pratschke, Johann; Sauer, Igor M.; Struecker, Benjamin

doi:10.3791/53029

Cited by 15 publications

(16 citation statements)

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“…Since the first description of whole‐liver de‐ and recellularization in 2010, great achievements in the field of liver bioengineering have been reported . Various decellularization protocols have been established in mouse, rat, ferret and human‐scale animals, such as sheep and pigs . Furthermore, the first protocols for decellularization of deceased human livers became available in 2017 in studies published by Verstegen et al .…”

Section: Livermentioning

confidence: 99%

“…Since the first description of whole-liver de-and recellularization in 2010, great achievements in the field of liver bioengineering have been reported [110,111]. Various decellularization protocols have been established in mouse, rat, ferret and human-scale animals, such as sheep and pigs [11,54,69,[112][113][114]. Furthermore, the first protocols for decellularization of deceased human livers became available in 2017 in studies published by Verstegen et al [115].Nevertheless, no systematic comparisons of the damage different decellularization protocols exerts on the extracellular matrix or on recellularization results are available.…”

Section: Livermentioning

confidence: 99%

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Strategies based on organ decellularization and recellularization

et al. 2019

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Summary Transplantation is the only curative treatment option available for patients suffering from end‐stage organ failure, improving their quality of life and long‐term survival. However, because of organ scarcity, only a small number of these patients actually benefit from transplantation. Alternative treatment options are needed to address this problem. The technique of whole‐organ decellularization and recellularization has attracted increasing attention in the last decade. Decellularization includes the removal of all cellular components from an organ, while simultaneously preserving the micro and macro anatomy of the extracellular matrix. These bioscaffolds are subsequently repopulated with patient‐derived cells, thus constructing a personalized neo‐organ and ideally eliminating the need for immunosuppression. However, crucial problems have not yet been satisfyingly addressed and remain to be resolved, such as organ and cell sources. In this review, we focus on the actual state of organ de‐ and recellularization, as well as the problems and future challenges.

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Section: Livermentioning

confidence: 99%

Section: Livermentioning

confidence: 99%

Strategies based on organ decellularization and recellularization

et al. 2019

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“…An interesting study showed that, with the specific protocol reported, HA perfusion lead to superior decellularization outcomes when compared to PV perfusion. It was also shown that the addition of oscillating pressure during decellularization facilitated residual DNA removal …”

Section: Whole Liver Decellularizationmentioning

confidence: 99%

Whole liver engineering: A promising approach to develop functional liver surrogates

Meng

Assiri

Dhar

et al. 2017

Liver International

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Liver donor shortage remains the biggest challenge for patients with end-stage liver failures. While bioartificial liver devices have been developed as temporary supports for patients waiting for transplantation, their applications have been limited clinically.Whole liver engineering is a biological scaffold based regenerative medicine approach that holds promise for developing functional liver surrogates. Significant advancements have been made since the first report in 2010. This review focuses on the recent achievements of whole liver engineering studies. K E Y W O R D Sdecellularization, endothelialization, recellularization, transplantation, whole liver engineering | INTRODUCTIONLiver is the largest internal organ responsible for important physiological functions, including vitamin storage, protein synthesis and detoxification. For patients with end-stage liver failures, that are often associated with hepatitis, bile duct-related diseases or liver cancers, liver transplantation has become the golden treatment. It provides better quality of life and cost effectiveness. The 5-year survival rate following liver transplantation is above 70%. However, the number of patients who needs a transplant still exceeds available donors. In the USA alone, it was reported that more than 16 000 patients need transplantation yearly but only 6000 liver transplantations are performed due to shortage of suitable donors.1 According to US Department of Health and Human Services, the shortage of eligible donors results in 18 deaths every day. There is a need for innovative approaches to develop functional liver surrogates for end-stage liver failure patients.Bioartificial liver devices (BAL) have been developed to temporarily function as surrogates for patients waiting for liver transplants. The BAL systems are extracorporeal, which consist of an artificial component (ie, the bioreactor) and a biological component (ie, hepatocytes).BAL systems have significantly prolonged the animal survival rate in preclinical studies and also have been applied in clinical trials. 2,3However, currently there are no strong evidence supporting the survival benefits of patients utilizing these devices and the incapability to prolong hepatocyte functions has limited their applications clinically. Figure 1 shows the concept of biological scaffold based whole liver engineering. | BioreactorBioreactors are designed to mimic the in vivo physiological environment such that an optimal growth condition is created for cells to repopulate the whole organ scaffolds. Several key components are required to build an appropriate bioreactor, including nutrient/waste exchange, temperature control, gas supply, real time monitoring of biomolecules of interest and organ-type specific stimuli. For example, the presence of air-liquid interface has been shown to induce ciliogenesis in tracheal regeneration 39 and physical stimuli such as ventilation were found beneficial to recellularized lung scaffold culture. 37Identifying specific stimuli that facilitate liver...

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“…Various methods for decellularization of animal livers by treatment with detergents or sodium cholate have been described. [4][5][6] The resulting extracellular matrix (ECM) harbors cytokines and growth factors which regulate various cellular processes. 7 It can be used as a scaffold for recellularization with human cells to obtain a functional organ model.…”

Section: Introductionmentioning

confidence: 99%

“…Methods for the decellularization of explanted livers have been described previously. 4,5 The extracellular matrices used here were obtained by excessive perfusion of a rat liver with 1% sodium deoxycholate. The liver is placed in a growth chamber and connected to the perfusion circuit, which consists of a peristaltic pump, a medium reservoir, a bubble trap and a pressure sensor.…”

mentioning

confidence: 99%

Study of Viral Vectors in a Three-dimensional Liver Model Repopulated with the Human Hepatocellular Carcinoma Cell Line HepG2

Hiller

Röhrs

Dehne

et al. 2016

JoVE

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This protocol describes the generation of a three-dimensional (3D) ex vivo liver model and its application to the study and development of viral vector systems. The model is obtained by repopulating the extracellular matrix of a decellularized rat liver with a human hepatocyte cell line. The model permits studies in a vascularized 3D cell system, replacing potentially harmful experiments with living animals. Another advantage is the humanized nature of the model, which is closer to human physiology than animal models.In this study, we demonstrate the transduction of this liver model with a viral vector derived from adeno-associated viruses (AAV vector). The perfusion circuit that supplies the 3D liver model with media provides an easy means to apply the vector. The system permits monitoring of the major metabolic parameters of the liver. For final analysis, tissue samples can be taken to determine the extent of recellularization by histological techniques. Distribution of the virus vector and expression of the delivered transgene can be analyzed by quantitative PCR (qPCR), Western blotting and immunohistochemistry. Numerous applications of the vector model in basic research and in the development of gene therapeutic applications can be envisioned, including the development of novel antiviral therapeutics, cancer research, and the study of viral vectors and their potential side effects.

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Procedure for Decellularization of Rat Livers in an Oscillating-pressure Perfusion Device

Cited by 15 publications

References 15 publications

Strategies based on organ decellularization and recellularization

Strategies based on organ decellularization and recellularization

Whole liver engineering: A promising approach to develop functional liver surrogates

Study of Viral Vectors in a Three-dimensional Liver Model Repopulated with the Human Hepatocellular Carcinoma Cell Line HepG2

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