| Controlled formation of heterotypic hepatic micro-organoids in anisotropic hydrogel microfibers for long-term preservation of liver-specific functions. | |
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MedLine Citation:
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PMID: 22906609 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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We have developed a hydrogel-based cell cultivation platform for forming 3D restiform hepatic micro-organoids consisting of primary rat hepatocytes and feeder cells (Swiss 3T3 cells). Sodium alginate solutions containing hepatocytes/3T3 cells were continuously introduced into a microfluidic channel to produce cell-incorporating anisotropic Ba-alginate hydrogel microfibers, where hepatocytes at the center were closely sandwiched by 3T3 cells. Hydrogel fiber-based cultivation under high oxygen tension enabled the formation of heterotypic micro-organoids with a length of up to 1 mm and a diameter of ∼50 μm, mimicking the hepatic cord structures found in the liver, while maintaining a high hepatocyte viability (∼80%) over 30 days. Long-term observation of up to 90 days revealed a significant enhancement of hepatic functions because of heterotypic and homotypic cell-cell interactions, including albumin secretion and urea synthesis as well as expression of hepatocyte-specific genes, compared with conventional monolayer culture and single cultivation in the hydrogel fibers. The encapsulated hepatic constructs were recovered as scaffold-free micro-organoids by enzymatically digesting the hydrogel matrices using alginate lyase. This technique for creating heterotypic micro-organoids with precisely ordered multiple cell types will be useful for the development of a new liver tissue engineering approach and may be applicable to the fabrication of extracorporeal bioartificial liver (BAL) devices and assessment tools for drug development and testing. |
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Authors:
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Masumi Yamada; Rie Utoh; Kazuo Ohashi; Kohei Tatsumi; Masayuki Yamato; Teruo Okano; Minoru Seki |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-8-17 |
Journal Detail:
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Title: Biomaterials Volume: - ISSN: 1878-5905 ISO Abbreviation: Biomaterials Publication Date: 2012 Aug |
Date Detail:
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Created Date: 2012-8-21 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8100316 Medline TA: Biomaterials Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2012 Elsevier Ltd. All rights reserved. |
Affiliation:
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Department of Applied Chemistry and Biotechnology, Graduate School of Engineering, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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