Biotechnology Challenges to In Vitro Maturation of Hepatic Stem Cells

Chen, Chen; Soto-Gutiérrez, Alejandro; Baptista, Pedro M.; Spee, Bart

doi:10.1053/j.gastro.2018.01.066

Cited by 92 publications

(91 citation statements)

References 147 publications

(155 reference statements)

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“…It is known that several other factors in the microenvironment are needed to improve this hepatic maturation, including co‐culture, smaller microgels produced with microfluidics, amongst others. [ 40 ] Interestingly, both the polarization markers MRP2 and ZO1, which are located at the apical membrane of a native hepatocyte and at the apical membrane or in close proximity thereof, respectively, [ 25,41 ] showed a different localization in organoids cultured in CNF hydrogel compared to MG. Polarization of cells is induced by the ECM in livers or by ECM mimicking materials in vitro and is very important for the function of the cells. [ 3 ] The needed apicobasal polarity can be found in both CNF hydrogel and MG, however, it was more pronounced in CNF but polarity was inversed.…”

Section: Discussionmentioning

confidence: 99%

Cellulose Nanofibril Hydrogel Promotes Hepatic Differentiation of Human Liver Organoids

Krüger

Oosterhoff

Wolferen

et al. 2020

Adv Healthcare Materials

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To replicate functional liver tissue in vitro for drug testing or transplantation, 3D tissue engineering requires representative cell models as well as scaffolds that not only promote tissue production but also are applicable in a clinical setting. Recently, adult liver‐derived liver organoids are found to be of much interest due to their genetic stability, expansion potential, and ability to differentiate toward a hepatocyte‐like fate. The current standard for culturing these organoids is a basement membrane hydrogel like Matrigel (MG), which is derived from murine tumor material and apart from its variability and high costs, possesses an undefined composition and is therefore not clinically applicable. Here, a cellulose nanofibril (CNF) hydrogel is investigated with regard to its potential to serve as an alternative clinical grade scaffold to differentiate liver organoids. The results show that its mechanical properties are suitable for differentiation with overall, either equal or improved, functionality of the hepatocyte‐like cells compared to MG. Therefore, and because of its defined and tunable chemical definition, the CNF hydrogel presents a viable alternative to MG for liver tissue engineering with the option for clinical use.

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Section: Discussionmentioning

confidence: 99%

Cellulose Nanofibril Hydrogel Promotes Hepatic Differentiation of Human Liver Organoids

Krüger

Oosterhoff

Wolferen

et al. 2020

Adv Healthcare Materials

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“…Many GF and small molecules play critical roles in the hepatic specification and stem cell maturation (Chen et al, 2018). TGF-α and EGF are just a few examples of liver autocrine GF signaling.…”

Section: Growth Factor Presentationmentioning

confidence: 99%

The role of extracellular matrix on liver stem cell fate: A dynamic relationship in health and disease

et al. 2019

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The liver stem cell niche is a specialized and dynamic microenvironment with biomechanical and biochemical characteristics that regulate stem cell behavior. This is feasible due to the coordination of a complex network of secreted factors, small molecules, neural, blood inputs and extracellular matrix (ECM) components involved in the regulation of stem cell fate (self-renewal, survival, and differentiation into more mature phenotypes like hepatocytes and cholangiocytes). In this review, we describe and summarize all the major components that play essential roles in the liver stem cell niche, in particular, growth factor signaling and the biomechanical properties of the ECM.

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“…Although multiple literature reports have adopted ES-derived hepatocytes, there are still some lingering ethical issues for some people and religious groups, [120] and more importantly, they are concerns with the robustness of their hepatic functions. [121] The iPS cells can be differentiated toward the hepatic lineage, improving the prospects in hepatology field and consequently their potential use in BAL devices. We mention hereafter only the works performed in the field of BAL.…”

Section: Liver Cell Sourcesmentioning

confidence: 99%

“…Therefore, ESCs and iPSCs remain the most promising approach to be explored for extracorporeal BAL. [121]…”

Section: Liver Cell Sourcesmentioning

confidence: 99%

Bioengineering Organs for Blood Detoxification

Legallais

Kim

Mihaila

et al. 2018

Adv Healthcare Materials

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For patients with severe kidney or liver failure the best solution is currently organ transplantation. However, not all patients are eligible for transplantation and due to limited organ availability, most patients are currently treated with therapies using artificial kidney and artificial liver devices. These therapies, despite their relative success in preserving the patients' life, have important limitations since they can only replace part of the natural kidney or liver functions. As blood detoxification (and other functions) in these highly perfused organs is achieved by specialized cells, it seems relevant to review the approaches leading to bioengineered organs fulfilling most of the native organ functions. There, the culture of cells of specific phenotypes on adapted scaffolds that can be perfused takes place. In this review paper, first the functions of kidney and liver organs are briefly described. Then artificial kidney/liver devices, bioartificial kidney devices, and bioartificial liver devices are focused on, as well as biohybrid constructs obtained by decellularization and recellularization of animal organs. For all organs, a thorough overview of the literature is given and the perspectives for their application in the clinic are discussed.

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Biotechnology Challenges to In Vitro Maturation of Hepatic Stem Cells

Cited by 92 publications

References 147 publications

Cellulose Nanofibril Hydrogel Promotes Hepatic Differentiation of Human Liver Organoids

Cellulose Nanofibril Hydrogel Promotes Hepatic Differentiation of Human Liver Organoids

The role of extracellular matrix on liver stem cell fate: A dynamic relationship in health and disease

Bioengineering Organs for Blood Detoxification

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