Preparation and culture of hepatocyte on gelatin microcarriers

Xu, Tao; Li, Shaolin; Yu, Yaoting

doi:10.1002/jbm.a.10277

Cited by 24 publications

(14 citation statements)

References 9 publications

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“…Alternatively, potentially resorbable biological beads that can provide a natural three‐dimensional environment to proliferate cells have been described,26 including those based on powdered acellular dermis27 or porous collagen beads that are formed after removal of an alginate carrier 17. Heavily cross‐linked (≫1%) gelatin beads have also been described 28…”

Section: Discussionmentioning

confidence: 99%

“…17 Heavily cross-linked (1%) gelatin beads have also been described. 28 In this study, we have examined a range of gelatin and gelatin/collagen composite beads with the aim of characterizing beads that would show suitable characteristics for direct use in tissue engineering and cell therapy applications. The emulsion method proved a suitable approach for making the beads and the treatments used in production did not lead to any apparent residual cytotoxicity.…”

Section: Discussionmentioning

confidence: 99%

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Preparation of resorbable collagen‐based beads for direct use in tissue engineering and cell therapy applications

Glattauer

White

Tsai

et al. 2009

J Biomedical Materials Res

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For tissue engineering and cell therapy applications, expansion of cells such as chondrocytes on beads in spinner culture can provide advantages compared with monolayer culture. The use of resorbable beads that can be included as an integral part of the construct provides the advantage of minimizing the extent of cell handling and eliminating a final trypsin treatment to detach cells from the bead. In this study, we have made various types of beads based on native collagen and denatured collagen (gelatin). The beads have been stabilized by different extents of glutaraldehyde cross-linking, and characterized by a combination of chemical analysis, thermal stability, and microscopy. In vitro examination in the presence and absence of chondrocytes showed that stability increased with the extent of crosslinking and could also be influenced by the manner of fabrication. On the basis of the in vitro stability studies, gelatin beads of a defined stability were shown to resorb over time in subcutaneous implants in nude mice compared with more stable demineralized bone particle (DMB) carriers. These data indicate that for direct use in tissue engineering or cell therapy applications, where resorbable beads can be used for cell expansion and then direct delivery of cells, it is possible to design suitable carrier beads with a range of stabilities that match the implant requirements.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Preparation of resorbable collagen‐based beads for direct use in tissue engineering and cell therapy applications

Glattauer

White

Tsai

et al. 2009

J Biomedical Materials Res

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“…The intraperitoneal transplantation of these hepatocyte-attached microcarriers resulted in successful replacement of liver functions in two different rodent models of genetic liver disorders [198]. Subsequently, collagencoated or peptide-modified cellulose [196,199], gelatin [200], and gelatin-chitosan composite [201] microcarrier chemistries have also been explored for their capacity to promote hepatocyte attachment. On the other hand, materials that are poorly cell adhesive like alginate [70] have been exploited for their utility in promoting hepatocyte-hepatocyte aggregation (e.g., spheroid formation) and hence hepatocyte stabilization within these scaffolds.…”

Section: Natural Scaffold Chemistry and Modificationsmentioning

confidence: 99%

Hepatic Tissue Engineering

Stevens

Schwartz

et al. 2014

Principles of Tissue Engineering

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Liver disease afflicts over 600 million people worldwide, 30 million of whom are Americans. Liver disease leads to the death of over 40,000 individuals in the United States every year. Liver failure can be generally separated into two major categories: fulminant hepatic failure, also referred to as acute liver failure, and chronic hepatic failure resulting from chronic end-stage liver disorders. The term fulminant hepatic failure is utilized for cases in which hepatic encephalopathy and impaired synthetic function (i.e., coagulopathy) develops within 26 weeks of the initial onset of jaundice. Hepatic encephalopathy is a neuropsychiatric condition, which can be divided into four stages ranging from minor effects such as mild confusion and sleep disorder, to deep coma. Although fulminant hepatic failure is relatively rare, with approximately 2,000 cases in the United States per year, it exhibits a high mortality rate of approximately 28% [1]. The major identified causes of fulminant hepatic failure include acetaminophen overdose, idiosyncratic drug reactions, and viral hepatitis A and B [1]. Of note, a recent multicenter etiology study showed that 17% of fulminant hepatic failure cases remained of indeterminate origin [2]. In addition to hepatic encephalopathy, other clinical manifestations of fulminant hepatic failure include bacterial and fungal infection, coagulopathy, as well as metabolic, cardiorespiratory, and hemodynamic abnormalities. Though spontaneous recovery has been observed due to the regenerative capacity of the liver, this type of recovery is difficult to predict, and rarely occurs in various etiologies, such as idiosyncratic drug toxicity and hepatitis B [1]. Liver transplantation is currently the only therapy shown to directly alter mortality, and therefore, is the standard of care in most clinical settings. As a result, all fulminant hepatic failure patients that meet the criteria for orthotopic liver transplant are immediately listed as United Network for Organ Sharing Status 1 (highest priority) upon presentation. Factors that preclude this designation are irreversible brain damage, unresponsive cerebral edema, uncontrollable sepsis, malignancy, and multisystem organ failure. Despite the effectiveness of liver transplant in improving short-term survival of fulminant hepatic failure patients, the utility of this approach remains limited due to the scarcity of donor organs.Liver failure due to chronic liver diseases, while exhibiting a longer time-course of disease pathogenesis, is much more common than fulminant failure, with chronic liver disease 951 Principles of Tissue Engineering. http://dx.

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“…Other naturally occurring materials that are not found in liver ECM, have also been utilized as substratum for hepatocyte culture. These include gelatin, 76 chitosan, 77,78 and alginate 79,80 or composites of these materials 11,81 . Additionally, matrix scaffolds based completely on synthetic materials such as polyglycolic acid, 82 polylactic acid, 83 polylactic‐coglycolic acid, 84 polyethylene oxide, 85 polyurethane, 86 polyethylene glycol, 87 and dextran sulfate 88 have also been fabricated.…”

Section: Naturally Occurring and Artificially Synthesized Extracellulmentioning

confidence: 99%

Factors influencing stem cell differentiation into the hepatic lineage in vitro

Heng

Yin

et al. 2005

J of Gastro and Hepatol

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A major area of research in transplantation medicine is the potential application of stem cells in liver regeneration. This would require well-defined and efficient protocols for directing the differentiation of stem cells into the hepatic lineage, followed by their selective purification and proliferation in vitro. The development of such protocols would reduce the likelihood of spontaneous differentiation of stem cells into divergent lineages upon transplantation, as well as reduce the risk of teratoma formation in the case of embryonic stem cells. Additionally, such protocols could provide useful in vitro models for studying hepatogenesis and liver metabolism. The development of pharmokinetic and cytotoxicity/genotoxicity screening tests for newly developed biomaterials and drugs, could also utilize protocols developed for the hepatic differentiation of stem cells. Hence, this review critically examines the various strategies that could be employed to direct the differentiation of stem cells into the hepatic lineage in vitro.

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Preparation and culture of hepatocyte on gelatin microcarriers

Cited by 24 publications

References 9 publications

Preparation of resorbable collagen‐based beads for direct use in tissue engineering and cell therapy applications

Preparation of resorbable collagen‐based beads for direct use in tissue engineering and cell therapy applications

Hepatic Tissue Engineering

Factors influencing stem cell differentiation into the hepatic lineage in vitro

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