論文 - 詳細
| RRC ID | 37929 |
|---|---|
| 著者 | Yamaza T, Alatas FS, Yuniartha R, Yamaza H, Fujiyoshi JK, Yanagi Y, Yoshimaru K, Hayashida M, Matsuura T, Aijima R, Ihara K, Ohga S, Shi S, Nonaka K, Taguchi T. |
| タイトル | In vivo hepatogenic capacity and therapeutic potential of stem cells from human exfoliated deciduous teeth in liver fibrosis in mice. |
| ジャーナル | Stem Cell Res Ther |
| Abstract |
INTRODUCTION:Liver transplantation is a gold standard treatment for intractable liver diseases. Because of the shortage of donor organs, alternative therapies have been required. Due to their potential to differentiate into a variety of mature cells, stem cells are considered feasible cell sources for liver regeneration. Stem cells from human exfoliated deciduous teeth (SHED) exhibit hepatogenic capability in vitro. In this study, we investigated their in vivo capabilities of homing and hepatocyte differentiation and therapeutic efficacy for liver disorders in carbon tetrachloride (CCl4)-induced liver fibrosis model mice. METHODS:We transplanted SHED into CCl4-induced liver fibrosis model mice through the spleen, and analyzed the in vivo homing and therapeutic effects by optical, biochemical, histological, immunological and molecular biological assays. We then sorted human leukocyte antigen-ABC (HLA-ABC)-positive cells from primary CCl4-damaged recipient livers, and analyzed their fusogenicity and hepatic characteristics by flow cytometric, genomic DNA, hepatocyte-specific gene assays. Furthermore, we examined the treatment effects of HLA-positive cells to a hepatic dysfunction by a secondary transplantation into CCl4-treated mice. RESULTS:Transplanted SHED homed to recipient livers, and expressed HLA-ABC, human hepatocyte specific antigen hepatocyte paraffin 1 and human albumin. SHED transplantation markedly recovered liver dysfunction and led to anti-fibrotic and anti-inflammatory effects in the recipient livers. SHED-derived HLA-ABC-positive cells that were sorted from the primary recipient liver tissues with CCl4 damage did not fuse with the host mouse liver cells. Sorted HLA-positive cells not only expressed human hepatocyte-specific genes including albumin, cytochrome P450 1A1, fumarylacetoacetase, tyrosine aminotransferase, uridine 5'-diphospho-glucuronosyltransferase, transferrin and transthyretin, but also secreted human albumin, urea and blood urea nitrogen. Furthermore, SHED-derived HLA-ABC-positive cells were secondary transplanted into CCl4-treated mice. The donor cells homed into secondary recipient livers, and expressed hepatocyte paraffin 1 and human albumin, as well as HLA-ABC. The secondary transplantation recovered a liver dysfunction in secondary recipients. CONCLUSIONS:This study indicates that transplanted SHED improve hepatic dysfunction and directly transform into hepatocytes without cell fusion in CCl4-treated mice, suggesting that SHED may provide a feasible cell source for liver regeneration. |
| 巻・号 | 6(1) |
| ページ | 171 |
| 公開日 | 2015-9-10 |
| DOI | 10.1186/s13287-015-0154-6 |
| PII | 10.1186/s13287-015-0154-6 |
| PMID | 26358689 |
| PMC | PMC4566368 |
| MeSH | Animals Biomarkers / metabolism Cell Differentiation* Cells, Cultured Child Dental Pulp / cytology HLA Antigens / genetics HLA Antigens / metabolism Hepatocytes / cytology* Hepatocytes / metabolism Humans Liver Cirrhosis / therapy* Mesenchymal Stem Cell Transplantation* Mesenchymal Stem Cells / cytology* Mesenchymal Stem Cells / metabolism Mice |
| IF | 5.116 |
| 引用数 | 32 |
| WOS 分野 | MEDICINE, RESEARCH & EXPERIMENTAL CELL BIOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | Hep G2(RCB1886) |