Document Detail


Controlled formation of heterotypic hepatic micro-organoids in anisotropic hydrogel microfibers for long-term preservation of liver-specific functions.
MedLine Citation:
PMID:  22906609     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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.
Authors:
Masumi Yamada; Rie Utoh; Kazuo Ohashi; Kohei Tatsumi; Masayuki Yamato; Teruo Okano; Minoru Seki
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-8-17
Journal Detail:
Title:  Biomaterials     Volume:  -     ISSN:  1878-5905     ISO Abbreviation:  Biomaterials     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-8-21     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8100316     Medline TA:  Biomaterials     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 Elsevier Ltd. All rights reserved.
Affiliation:
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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