Enhanced maintenance and functions of rat hepatocytes induced by combination of on-site oxygenation and coculture with fibroblasts

Nishikawa, Masaki; Kojima, Naoya; Komori, Kikuo; Yamamoto, Takatoki; Fujii, Teruo; Sakai, Yasuyuki

doi:10.1016/j.jbiotec.2007.08.041

Cited by 60 publications

(63 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…2). This albumin secretion, as previously observed on HepG2-3T3 fibroblast cocultures on a PDMS membrane (23). In the present study, oxygen had a direct as well as indirect influence on albumin secretion.…”

Section: Morphologies Of Fetal Liver Cells In the Different Oh Usa)supporting

confidence: 92%

“…The PDMS plates were prepared as previously described phosphate (Wako), antibiotic/antimycotic solution (Invitrogen), 1% MEM nonessential amino acid solution (23,24). A PDMS membrane (thickness: 1.5 mm) was attached and clamped between a 24-well polycarbonate (Invitrogen), and 10% fetal bovine serum (FBS; Gemini Bio-Product, CA, USA).…”

Section: (Fgf-1) and Fibroblast Growth Factor-4 (Fgf-4)] (34)mentioning

confidence: 99%

“…The oxygen concentration directly influenced the thickness of the latcells. This avoids the quick impoverishment of oxygen in the culture medium (23). The silicone elastomer is a ter layer; a low oxygen environment induced mesenchymal cell growth and ECM secretion as observed in vivo good candidate to cultivate mammalian cells due to its biocompatibility (3,28) as well as its high gas diffusion (8,33), making the tissue thicker (Fig.…”

Section: Morphologies Of Fetal Liver Cells In the Different Oh Usa)mentioning

confidence: 99%

See 2 more Smart Citations

Direct Oxygen Supply with Polydimethylsiloxane (PDMS) Membranes Induces a Spontaneous Organization of Thick Heterogeneous Liver Tissues from Rat Fetal Liver Cells in Vitro

et al. 2012

Self Cite

View full text Add to dashboard Cite

Oxygen is a vital nutrient for growth and maturation of in vitro cells (e.g., adult hepatocytes). We previously demonstrated that direct oxygenation through a polydimethylsiloxane (PDMS) membrane increases the oxygen supply to cell cultures and improves hepatocyte functions. In this study, we removed limits on oxygen supply to fetal rat liver cells through the use of direct oxygenation through a PDMS membrane to investigate in vitro growth and maturation. We chose fetal liver cells because they are considered a feasible source of liver progenitor cells for regenerative medicine therapy due to their highly efficient maturation and proliferation. Cells from 17-day-old pregnant rats were cultured under 5% and 21% oxygen atmospheres. Some cells were first cultured under 5% oxygen, and then switched to a 21% oxygen atmosphere. When oxygen supply was enhanced by a PDMS membrane, the rat fetal liver cells organized into a complex tissue composed of an epithelium of hepatocytes above a mesenchyme-like tissue. The thickness of this supportive tissue was directly correlated to oxygen concentration and was thicker under 5% oxygen. When cultures were switched from 5% to 21% oxygen, lumen-containing structures were formed in the thick mesenchymal-like tissue and the albumin secretion rate increased. In addition, cells adapted their glycolytic activity to the oxygen concentrations. This system promoted the formation of a functional and organized thick tissue suitable for use in regenerative medicine.

show abstract

Section: Morphologies Of Fetal Liver Cells In the Different Oh Usa)supporting

confidence: 92%

Section: (Fgf-1) and Fibroblast Growth Factor-4 (Fgf-4)] (34)mentioning

confidence: 99%

Section: Morphologies Of Fetal Liver Cells In the Different Oh Usa)mentioning

confidence: 99%

See 1 more Smart Citation

Direct Oxygen Supply with Polydimethylsiloxane (PDMS) Membranes Induces a Spontaneous Organization of Thick Heterogeneous Liver Tissues from Rat Fetal Liver Cells in Vitro

et al. 2012

Self Cite

View full text Add to dashboard Cite

show abstract

“…Most microfluidic devices reported in literature are made of PDMS, a gas permeable elastomer [30,[67][68][69]. Therefore, the computational model presented in Section 4.2 can be refined by considering the inward oxygen flux through PDMS, which is given by the following expression [67,70]:…”

Section: Cfd Model Refinement: Oxygen Diffusion Through Pdms Wallsmentioning

confidence: 99%

Design Criteria for Generating Physiologically Relevant In Vitro Models in Bioreactors

2014

View full text Add to dashboard Cite

Abstract:In this paper, we discuss the basic design requirements for the development of physiologically meaningful in vitro systems comprising cells, scaffolds and bioreactors, through a bottom up approach. Very simple micro-and milli-fluidic geometries are first used to illustrate the concepts, followed by a real device case-study. At each step, the fluidic and mass transport parameters in biological tissue design are considered, starting from basic questions such as the minimum number of cells and cell density required to represent a physiological system and the conditions necessary to ensure an adequate nutrient supply to tissues. At the next level, we consider the use of three-dimensional scaffolds, which are employed both for regenerative medicine applications and for the study of cells in environments which better recapitulate the physiological milieu. Here, the driving need is the rate of oxygen supply which must be maintained at an appropriate level to ensure cell viability throughout the thickness of a scaffold. Scaffold and bioreactor design are both critical in defining the oxygen profile in a cell construct and are considered together. We also discuss the oxygen-shear stress trade-off by considering the levels of mechanical stress required for hepatocytes, which are the limiting cell type in a multi-organ model. Similar considerations are also made for glucose consumption in cell constructs. Finally, the allometric approach for generating multi-tissue systemic models using bioreactors is described.

show abstract

“…Many studies tried to simulate the physiological organization of liver tissue by recruitment of the nonparenchymal cells ͑NPCs͒ into the liver function unit in EBAL, and it has been shown that the hepatic functions can be preserved for long term in the coculture system. [33][34][35][36][37] Some soluble factors, which are believed to have important influence on the differentiated phenotype of hepatocytes, can continuously be generated as long as the heterogeneous cells' interactions are maintained in the coculture system. Chia et al, 38 cocultured a rat primary hepatocyte with a mouse embryonic fibroblast cell line, NIH3T3 in a threedimensional ͑3D͒ microencapsule formation and found that the direct interactions between the cells and their secretion of various soluble factors play an important role in enhancing the hepatocytes' function.…”

Section: B Coculturementioning

confidence: 99%

Current development of bioreactors for extracorporeal bioartificial liver (Review)

et al. 2010

View full text Add to dashboard Cite

The research and development of extracorporeal bioartificial liver is gaining pace in recent years with the introduction of a myriad of optimally designed bioreactors with the ability to maintain long-term viability and liver-specific functions of hepatocytes. The design considerations for bioartificial liver are not trivial; it needs to consider factors such as the types of cell to be cultured in the bioreactor, the bioreactor configuration, the magnitude of fluid-induced shear stress, nutrients' supply, and wastes' removal, and other relevant issues before the bioreactor is ready for testing. This review discusses the exciting development of bioartificial liver devices, particularly the various types of cell used in current reactor designs, the state-of-the-art culturing and cryopreservation techniques, and the comparison among many today's bioreactor configurations. This review will also discuss in depth the importance of maintaining optimal mass transfer of nutrients and oxygen partial pressure in the bioreactor system. Finally, this review will discuss the commercially available bioreactors that are currently undergoing preclinical and clinical trials.

show abstract

Enhanced maintenance and functions of rat hepatocytes induced by combination of on-site oxygenation and coculture with fibroblasts

Cited by 60 publications

References 36 publications

Direct Oxygen Supply with Polydimethylsiloxane (PDMS) Membranes Induces a Spontaneous Organization of Thick Heterogeneous Liver Tissues from Rat Fetal Liver Cells in Vitro

Direct Oxygen Supply with Polydimethylsiloxane (PDMS) Membranes Induces a Spontaneous Organization of Thick Heterogeneous Liver Tissues from Rat Fetal Liver Cells in Vitro

Design Criteria for Generating Physiologically Relevant In Vitro Models in Bioreactors

Current development of bioreactors for extracorporeal bioartificial liver (Review)

Contact Info

Product

Resources

About