Hepatocyte and Kupffer Cells Co-cultured on Micropatterned Surfaces to Optimize Hepatocyte Function

Zinchenko, Yekaterina S.; Schrum, Laura W.; Clemens, Mark G.; Coger, Robin N.

doi:10.1089/ten.2006.12.751

Cited by 76 publications

(60 citation statements)

References 23 publications

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“…The type of micropattern used can strongly affect the culture fate [72,77], because it will determine diffusion rates and level of separation or contact between cell populations. Owing to cell polarization, exact positioning may be needed for mammalian cell studies to ensure that population contact is made via the correct cell surface [88].…”

Section: Degree Of Contact Between Populationsmentioning

confidence: 99%

Co-culture systems and technologies: taking synthetic biology to the next level

Goers

Freemont

Polizzi

2014

J. R. Soc. Interface.

516

368

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Co-culture techniques find myriad applications in biology for studying natural or synthetic interactions between cell populations. Such techniques are of great importance in synthetic biology, as multi-species cell consortia and other natural or synthetic ecology systems are widely seen to hold enormous potential for foundational research as well as novel industrial, medical and environmental applications with many proof-of-principle studies in recent years. What is needed for co-cultures to fulfil their potential? Cell-cell interactions in cocultures are strongly influenced by the extracellular environment, which is determined by the experimental set-up, which therefore needs to be given careful consideration. An overview of existing experimental and theoretical co-culture set-ups in synthetic biology and adjacent fields is given here, and challenges and opportunities involved in such experiments are discussed. Greater focus on foundational technology developments for co-cultures is needed for many synthetic biology systems to realize their potential in both applications and answering biological questions.

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Section: Degree Of Contact Between Populationsmentioning

confidence: 99%

Co-culture systems and technologies: taking synthetic biology to the next level

Goers

Freemont

Polizzi

2014

J. R. Soc. Interface.

516

368

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“…The importance of nonparenchymal cells to mount a response to a lipopolysaccharide (LPS) challenge was demonstrated when these cells were removed from the PHH culture by an additional purification step (Percoll purification) (15). It was recently shown that direct contact between hepatocytes and Kupffer cells affects cell function and viability of both types of cells (16).…”

Section: Hepatocyte Preparation and Culturementioning

confidence: 99%

Insulin Decreases Inflammatory Signal Transcription Factor Expression in Primary Human Liver Cells after LPS Challenge

Jeschke

Klein

Thasler

et al. 2008

Mol Med

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Hepatic homeostasis is essential for survival in critically ill and burned patients. Insulin administration improves survival and decreases infections in these patients. To determine the molecular mechanisms, the aim of the present study was to establish a stress model using primary human hepatocytes (PHHs) and to study the effects of insulin on the hepatic inflammatory signaling cascade. Liver tissue was obtained from general surgical patients, and PHHs were isolated and maintained in culture. Primary hepatocyte cultures were challenged with various doses of lipopolysaccharide (LPS), and the inflammatory signal transcription cascade was determined by real-time PCR. In subsequent experiments, primary hepatocyte cultures were challenged with LPS and insulin was added in various doses. Glucose was determined by colorimetric assays. PHHs treated with 100 µg/mL LPS showed a profound inflammatory reaction with increased expression of interleukin (IL)-6, IL-10, IL-1β, tumor necrosis factor (TNF), and signal transducer and activator of transcription 5 (STAT-5). Insulin at 10 IU/mL significantly decreased IL-6, TNF, and IL-1β at pretranslational levels, an effect associated with decreased STAT-5 mRNA expression (P < 0.05). Glucose concentration and cellular metabolic activity were not different between controls and insulin-treated cells. Based on our results, we suggest that primary hepatocyte cultures can be used to study the effect of LPS on the inflammatory cascade. Insulin decreases hepatic cytokine expression, which is associated with decreased STAT-5 expression.

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“…1 Hepatocytes cultured in monolayers (HMs) lose their phenotypic functions and suffer from mRNA degradation within 24 h of their removal from the liver. [2][3][4] Monolayers of liver sinusoidal endothelial cells (LSECs) 5 and Kupffer cells (KCs) 6 also rapidly dedifferentiate within a few days in vitro. Although hepatocytes cultured in a collagen sandwich (CS) or two-dimensional (2D) cocultures have been shown to exhibit stable expression of hepatic markers, 3,7-9 they do not emulate hepatic architecture in vivo.…”

mentioning

confidence: 99%

Designing a Multicellular Organotypic 3D Liver Model with a Detachable, Nanoscale Polymeric Space of Disse

Larkin

Rodrigues²,

Murali³

et al. 2013

Tissue Engineering Part C: Methods

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The design of in vitro models that mimic the stratified multicellular hepatic microenvironment continues to be challenging. Although several in vitro hepatic cultures have been shown to exhibit liver functions, their physiological relevance is limited due to significant deviation from in vivo cellular composition. We report the assembly of a novel three-dimensional (3D) organotypic liver model incorporating three different cell types (hepatocytes, liver sinusoidal endothelial cells, and Kupffer cells) and a polymeric interface that mimics the Space of Disse. The nanoscale interface is detachable, optically transparent, derived from self-assembled polyelectrolyte multilayers, and exhibits a Young's modulus similar to in vivo values for liver tissue. Only the 3D liver models simultaneously maintain hepatic phenotype and elicit proliferation, while achieving cellular ratios found in vivo. The nanoscale detachable polymeric interfaces can be modulated to mimic basement membranes that exhibit a wide range of physical properties. This facile approach offers a versatile new avenue in the assembly of engineered tissues. These results demonstrate the ability of the tri-cellular 3D cultures to serve as an organotypic hepatic model that elicits proliferation and maintenance of phenotype and in vivo-like cellular ratios.

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Hepatocyte and Kupffer Cells Co-cultured on Micropatterned Surfaces to Optimize Hepatocyte Function

Cited by 76 publications

References 23 publications

Co-culture systems and technologies: taking synthetic biology to the next level

Co-culture systems and technologies: taking synthetic biology to the next level

Insulin Decreases Inflammatory Signal Transcription Factor Expression in Primary Human Liver Cells after LPS Challenge

Designing a Multicellular Organotypic 3D Liver Model with a Detachable, Nanoscale Polymeric Space of Disse

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