Recellularization via the bile duct supports functional allogenic and xenogenic cell growth on a decellularized rat liver scaffold

Hassanein, Wessam; Uluer, Mehmet C.; Langford, John; Woodall, Jhade D.; Cimeno, Arielle; Dhru, Urmil; Werdesheim, Avraham; Harrison, Joshua; Rivera-Pratt, Carlos; Klepfer, Stephen; Khalifeh, Ali; Buckingham, Bryan; Brazio, Philip S.; Parsell, Dawn; Klassen, Charlie; Drachenberg, Cinthia; Barth, Rolf N.; LaMattina, John C.

doi:10.1080/15476278.2016.1276146

Cited by 37 publications

(32 citation statements)

References 34 publications

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“…Studies investigating whether this approach is feasible are lacking. Several studies have successfully achieved reendothelialization (with or without coating the remaining ECM) and parenchymatous recellularization of liver scaffolds in vitro [8,20,64,73,112,113,[116][117][118][119][120][121][122][123]. Various cell types, such as hepatocytes (e.g.…”

Section: Livermentioning

confidence: 99%

“…The existing studies have achieved an in vitro cultivation of the neo-livers for up to 28 days and revealed restored functionality (e.g. albumin secretion, urea production, ammonium metabolism and enzyme regulation), drug metabolism and viability of the seeded cells [8,20,64,73,79,81,112,113,[116][117][118][119]121]. According to Robertson et al, recellularized livers produce albumin and metabolize midazolam until the end of their study at 28 days.…”

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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“…Ko et al., utilized four vasculatures for the scaffold re‐endothelialization and such multi‐route approach might also facilitate the parenchymal repopulation efficiency. In addition to the vasculature, bile ducts were also utilized for parenchymal recellularization and showed encouraging results . Novel approaches that would increase the recellularization uniformity are of high interests.…”

Section: Liver Scaffold Recellularizationmentioning

confidence: 99%

“…In addition to the vasculature, bile ducts were also utilized for parenchymal recellularization and showed encouraging results. 90 Novel approaches that would increase the recellularization uniformity are of high interests.…”

Section: Recellularization With Hepatocyte and Nonparenchymal Cellsmentioning

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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“…Recent studies using in vitro 3D hepatocyte culture include systems based on microcarriers [3], hollow fibers [4][5][6], decellularized liver scaffolds [7][8][9], spheroidal aggregates [10][11][12][13], cell sheets [14][15][16], microfluidic chips [17][18][19][20], and 3D bioprinted cultures [21][22][23][24]. Despite the advantages of increased hepatocyte viability compared to 2D cultures, such systems share a common shortcoming.…”

Section: Introductionmentioning

confidence: 99%

3D Culture System for Liver Tissue Mimicking Hepatic Plates for Improvement of Human Hepatocyte (C3A) Function and Polarity

Jia

Cheng

Jiang

et al. 2020

BioMed Research International

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In vitro 3D hepatocyte culture constitutes a core aspect of liver tissue engineering. However, conventional 3D cultures are unable to maintain hepatocyte polarity, functional phenotype, or viability. Here, we employed microfluidic chip technology combined with natural alginate hydrogels to construct 3D liver tissues mimicking hepatic plates. We comprehensively evaluated cultured hepatocyte viability, function, and polarity. Transcriptome sequencing was used to analyze changes in hepatocyte polarity pathways. The data indicate that, as culture duration increases, the viability, function, polarity, mRNA expression, and ultrastructure of the hepatic plate mimetic 3D hepatocytes are enhanced. Furthermore, hepatic plate mimetic 3D cultures can promote changes in the bile secretion pathway via effector mechanisms associated with nuclear receptors, bile uptake, and efflux transporters. This study provides a scientific basis and strong evidence for the physiological structures of bionic livers prepared using 3D cultures. The systems and cultured liver tissues described here may serve as a better in vitro 3D culture platform and basic unit for varied applications, including drug development, hepatocyte polarity research, bioartificial liver bioreactor design, and tissue and organ construction for liver tissue engineering or cholestatic liver injury.

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Recellularization via the bile duct supports functional allogenic and xenogenic cell growth on a decellularized rat liver scaffold

Cited by 37 publications

References 34 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

3D Culture System for Liver Tissue Mimicking Hepatic Plates for Improvement of Human Hepatocyte (C3A) Function and Polarity

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