論文 - 詳細
| RRC ID | 44191 |
|---|---|
| 著者 | Iwamuro M, Shiraha H, Nakaji S, Furutani M, Kobayashi N, Takaki A, Yamamoto K. |
| タイトル | A preliminary study for constructing a bioartificial liver device with induced pluripotent stem cell-derived hepatocytes. |
| ジャーナル | Biomed Eng Online |
| 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. |
| 巻・号 | 11 |
| ページ | 93 |
| 公開日 | 2012-12-7 |
| DOI | 10.1186/1475-925X-11-93 |
| PII | 1475-925X-11-93 |
| PMID | 23217363 |
| PMC | PMC3549893 |
| MeSH | Animals Cell Culture Techniques / instrumentation* Cell Differentiation Cell Line Equipment Design Equipment Failure Analysis Hepatocytes / cytology* Hepatocytes / physiology* Liver, Artificial* Mice Organ Culture Techniques / instrumentation Pilot Projects Pluripotent Stem Cells / cytology* Pluripotent Stem Cells / physiology* Tissue Scaffolds* |
| IF | 2.059 |
| 引用数 | 15 |
| WOS 分野 | ENGINEERING, BIOMEDICAL |
| リソース情報 | |
| ヒト・動物細胞 | iPS-MEF-Ng-20D-17(APS0001) |