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Bioprinted Liver Tissues Generate Organ-Level Responses

by • July 12, 2016 • No Comments

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With new astounding advancements in bioprinting, of printing a heart structure in zero gravity to that successfully testing a bioprinter for stem cells, it is no surprise that the innovation is actively being applied to medical trials with real-world applications, and yielding ingenious outcomes for the community. In a new study funded internally by Roche Pharmaceuticals and Organovo Holdings Inc., bioprinted 3D human liver tissues were evaluated for their future use as durable, multi-cellular versions of effortless human liver tissue. As a outcome, the combination of patient-derived major cells with bioprinting innovation for the initially time has confirmed excellent performance in terms of mimicking human drug response in a known target organ at the tissue level.

Until newly, fabrication methods that enabled regulated spatial patterning of two or additional cell types were limited to two-dimensional cultures or cultures that were a few cell layers thick. In a ingenious feat, 3D bioprinting affords a means of fabricating tissue that is both spatially patterned and sufficiently three-dimensional, allowing for histological and biochemical assessments. Thusly, a fully human in vitro process comprising multiple liver cell types in a described spatial pattern that can be utilized to gather both histopathological and biochemical data has the future to provide worthwhile insights of the human tissue response in the pre-clinical setting, preceding costly human trials are initiated.

In this particular study, 3D liver tissues comprised of cryopreserved major human hepatocytes, hepatic stellates, and human umbilical vein endothelial cells (HUVEC) cells were manufactured by Organovo. Separate high density bio-inks comprising parenchymal cells, created of 100% cellular paste, produced via compaction, were made and loaded into separate heads of the NovoGen BioprinterĀ®Instrument. Fabrication of the liver tissues was enabled by additive making, that allowed the cellular inputs, spatial distribution, and geometry to be described with high precision. In this instance, the overall tissue structure does not fully recapitulate the native liver lobule, yet the presence and organization of multiple cell types inside the compartmentalized structure of the 3D liver tissues have proven to play a worthwhile role in preserving liver-specific functions.

Throughout the trial, the bioprinted tissues retained the compartmentalization of parenchymal and non-parenchymal components built at the time of fabrication. The tissues in addition condensed and reversioned over time, yielding stable 3D structures, dense tissue-like cellularity, and no evidence of necrosis. Amazingly, lipid storage space and glycogen storage space, two functions synonymous with hepatocytes in vivo, were in addition demonstrated in the bioprinted liver tissues after maturation. Comparison of specific staining between bioprinted liver tissues and native human liver biopsy in addition showed much like patterns of expression. In addition, to investigate the talent of the tissues to be utilized as a version of drug induced liver injury (DILI), researchers in addition tested their response to a known hepatotoxicant compared to a non-toxic relative. Taken all together, the outcomes suggest that 3D liver tissues may be a valuable addition to the pre-clinical toxicity pipeline.

These unprecedented outcomes confirm the sustained vitalent and functionality of 3D liver tissues over time as well as their clear excellentity over standard 2D cultures. Here, researchers have demonstrated that 3D bioprinted liver tissues can both effectively version DILI and distinguish between highly related compounds with differential profile. Overall, the trial has shown that this one-of-a-kind 3D version comprising multiple relevant liver cell types allows for for the study of the tissue response to insult beyond easy cytotoxicity, allowing the meacertainment of cell type specific responses as well as in vitro histological assessment over extended time in culture.

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