Analysis of transdifferentiation of hematopoietic stem cells into pancreatic endocrine cells using a single cell transplantation technique
| Project/Area Number |
16590935
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Mie University |
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Principal Investigator |
MASUYA Masahiro Mie University, Hospital, Lecturer, 医学部附属病院, 講師 (30281083)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2004: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | hemaopoietic stem cell / single cell transplantation / carbon tetrachloride / hepatic stellate cell / 可塑性 / 肝細胞 |
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| Research Abstract |
We have reported that glomerular mesangial cells in kidney and microglial cells and perivascular-pericyte-like cells in infracted brain are derived from hematopoietic stem cells (HSCs) using chimeric mice generated by transplantation of single enhanced green fluorescent protein (EGFP) -marked lineage negative (Lin^-) Sca-1^+ c-kit^+ CD34^- cells (single cell transplanted mice). It has been reported that oval cells in the liver may differentiate into several lineages including hepatocytes, biliary cells, endocrine and exocrine pancreatic cells, and intestinal epithelial cells. Moreover, oval cells express CD34, Thy-1, c-kit and flt-3 receptor, all of which are also found in HSCs. From these findings, we hypothesized that endocrine pancreatic cells are of HSC origin. To test this hypothesis, we established chronic liver injury model in transplanted mice induced by carbon tetrachloride (CCl4) ; CCl4 was injected into single cell transplanted mice intraperitoneally twice a week for 3 months. We examined the presence of oval cells in the liver and found a lot of EGFP^+ cells in injured liver especially in sinusoid. However, these cells were not oval cells. We tried to clarify the nature of these EGFP^+ cells using the indirect immunofluorescence method. Majority of EGFP^+ cells were negative for CD45 antigen and some cells were stained with oil-red O. Moreover, some other cells were positive for α-smooth muscle actin and glial fibrillary acidic protein. These findings suggest that the phenotype of EGFP^+ cells is consistent with that of hepatic stellate cells and that hepatic stellate cells might be from HSCs. Because hepatic stellate cells play an important role in pathogenesis of liver fibrosis, portal hypertension and fulminant hepatitis, we expect that the results from our examination can contribute to make new treatment strategies for these disorders.
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Report
(3 results)
Research Products
(20 results)
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[Journal Article] Dysregulation of granulocyte, erythrocyte, and NK cell lineages in Fli-1 gene-targeted mice.2005
Author(s)
Masuya M, Mousa O, Abe T, Deguchi T, Higuchi T, Ebihara Y, Spyropoulos DD, Watson DK, Ogawa M
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Journal Title
Blood 105・1
Pages: 95-102
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] A putative role for histone deacetylase in the differentiation of human erythroid cells.2005
Author(s)
Fujieda A, Katayama N, Ohishi K, Yamamura K, Shibasaki T, Sugimoto Y, Miyata E, Nishii K, Masuya M, Ueda H, Nakajima H, Shiku H
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Journal Title
Int J Oncol 27・3
Pages: 743-748
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] A novel role for Notch ligand Delta-1 as a regulator of human langerhans cell development from blood monocytes.2005
Author(s)
Hoshino N, Katayama N, Shibasaki T, Ohishi K, Nishioka J, Masuya M, Miyahara Y, Hayashida M, Shimomura D, Kato T, Nakatani K, Nishii K, Kuribayashi K, Nobori T, Shiku H
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Journal Title
J Leukoc Biol 78・4
Pages: 921-929
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] IL-4 and IL-10 synergistically inhibit survival of human blood monocytes supported by GM-CSF.2005
Author(s)
Miyashita H, Katayama N, Fujieda A, Shibasaki T, Yamamura K, Sugimoto Y, Miyata E, Ohishi K, Nishii K, Masuya M, Shiku H
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Journal Title
Int J Oncol 26・3
Pages: 731-735
Description
「研究成果報告書概要(欧文)」より
Related Report
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