A preliminary study for constructing a bioartificial liver device with induced pluripotent stem cell-derived hepatocytes

Masaya Iwamuro, Hidenori Shiraha, Shuhei Nakaji, Masumi Furutani, Naoya Kobayashi, Akinobu Takaki, Kazuhide Yamamoto

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Background: Bioartificial liver systems, designed to support patients with liver failure, are composed of bioreactors and functional hepatocytes. Immunological rejection of the embedded hepatocytes by the host immune system is a serious concern that crucially degrades the performance of the device. Induced pluripotent stem (iPS) cells are considered a desirable source for bioartificial liver systems, because patient-derived iPS cells are free from immunological rejection. The purpose of this paper was to test the feasibility of a bioartificial liver system with iPS cell-derived hepatocyte-like cells.Methods: Mouse iPS cells were differentiated into hepatocyte-like cells by a multi-step differentiation protocol via embryoid bodies and definitive endoderm. Differentiation of iPS cells was evaluated by morphology, PCR assay, and functional assays. iPS cell-derived hepatocyte-like cells were cultured in a bioreactor module with a pore size of 0.2 μm for 7 days. The amount of albumin secreted into the circulating medium was analyzed by ELISA. Additionally, after a 7-day culture in a bioreactor module, cells were observed by a scanning electron microscope.Results: At the final stage of the differentiation program, iPS cells changed their morphology to a polygonal shape with two nucleoli and enriched cytoplasmic granules. Transmission electron microscope analysis revealed their polygonal shape, glycogen deposition in the cytoplasm, microvilli on their surfaces, and a duct-like arrangement. PCR analysis showed increased expression of albumin mRNA over the course of the differentiation program. Albumin and urea production was also observed. iPS-Heps culture in bioreactor modules showed the accumulation of albumin in the medium for up to 7 days. Scanning electron microscopy revealed the attachment of cell clusters to the hollow fibers of the module. These results indicated that iPS cells were differentiated into hepatocyte-like cells after culture for 7 days in a bioreactor module with a pore size of 0.2 μm.Conclusion: We consider the combination of a bioreactor module with a 0.2-μm pore membrane and embedded hepatocytes differentiated from iPS cells to be a promising option for bioartificial liver systems. This paper provides the basic concept and preliminary data for an iPS cell-oriented bioartificial liver system.PACS code: 87. Biological and medical physics, 87.85.-d Biomedical engineering, 87.85.Lf Tissue engineering, 87.85.Tu Modeling biomedical systems.

Original languageEnglish
Article number93
JournalBioMedical Engineering Online
Volume11
DOIs
Publication statusPublished - Dec 7 2012

Fingerprint

Artificial Liver
Induced Pluripotent Stem Cells
Stem cells
Liver
Hepatocytes
Bioreactors
Equipment and Supplies
Albumins
Pore size
Circulating media
Assays
Electron microscopes
Electrons
Biomedical Engineering
Embryoid Bodies
Cytoplasmic Granules
Picture archiving and communication systems
Polymerase Chain Reaction
Endoderm
Biomedical engineering

Keywords

  • Antibody-mediated rejection
  • Bioartificial liver system
  • Hepatocyte differentiation
  • Hollow fiber bioreactor
  • Induced pluripotent stem cells

ASJC Scopus subject areas

  • Biomedical Engineering
  • Radiological and Ultrasound Technology
  • Radiology Nuclear Medicine and imaging
  • Biomaterials

Cite this

A preliminary study for constructing a bioartificial liver device with induced pluripotent stem cell-derived hepatocytes. / Iwamuro, Masaya; Shiraha, Hidenori; Nakaji, Shuhei; Furutani, Masumi; Kobayashi, Naoya; Takaki, Akinobu; Yamamoto, Kazuhide.

In: BioMedical Engineering Online, Vol. 11, 93, 07.12.2012.

Research output: Contribution to journalArticle

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AU - Takaki, Akinobu

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