Abstract
Transplantation of hepatocytes or hepatocyte-like cells of extrahepatic origin is a promising strategy for treatment of acute and chronic liver failure. We examined possible utility of hepatocyte-like cells induced from bone marrow cells for such a purpose. Clonal cell lines were established from the bone marrow of two different rat strains. One of these cell lines, rBM25/S3 cells, grew rapidly (doubling time, ∼24 hours) without any appreciable changes in cell properties for at least 300 population doubling levels over a period of 300 days, keeping normal diploid karyotype. The cells expressed CD29, CD44, CD49b, CD90, vimentin, and fibronectin but not CD45, indicating that they are of mesenchymal cell origin. When plated on Matrigel with hepatocyte growth factor and fibroblast growth factor-4, the cells efficiently differentiated into hepatocyte-like cells that expressed albumin, cytochrome P450 (CYP) 1A1, CYP1A2, glucose 6-phosphatase, tryptophane-2,3-dioxygenase, tyrosine aminotransferase, hepatocyte nuclear factor (HNF)1α, and HNF4α. Intrasplenic transplantation of the differentiated cells prevented fatal liver failure in 90%-hepatectomized rats. In conclusion, a clonal stem cell line derived from adult rat bone marrow could differentiate into hepatocyte-like cells, and transplantation of the differentiated cells could prevent fatal liver failure in 90%-hepatectomized rats. The present results indicate a promising strategy for treating human fatal liver diseases.
| Original language | English |
|---|---|
| Pages (from-to) | 2855-2863 |
| Number of pages | 9 |
| Journal | Stem Cells |
| Volume | 25 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - Nov 2007 |
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Keywords
- Clonal stem cell lines
- Hepatocyte-like cells
- Intrasplenic transplantation
- Mass production
- Rat bone marrow
ASJC Scopus subject areas
- Cell Biology
Cite this
Isolation of a bone marrow-derived stem cell line with high proliferation potential and its application for preventing acute fatal liver failure. / Miyazaki, Masahiro; Hardjo, Marhaen; Masaka, Takuro; Tomiyama, Koji; Mahmut, Naila; Medina, Reinhold J.; Niida, Aya; Sonegawa, Hiroyuki; Du, Gang; Yong, Rong; Takaishi, Mikiro; Sakaguchi, Masakiyo; Huh, Nam Ho.
In: Stem Cells, Vol. 25, No. 11, 11.2007, p. 2855-2863.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Isolation of a bone marrow-derived stem cell line with high proliferation potential and its application for preventing acute fatal liver failure
AU - Miyazaki, Masahiro
AU - Hardjo, Marhaen
AU - Masaka, Takuro
AU - Tomiyama, Koji
AU - Mahmut, Naila
AU - Medina, Reinhold J.
AU - Niida, Aya
AU - Sonegawa, Hiroyuki
AU - Du, Gang
AU - Yong, Rong
AU - Takaishi, Mikiro
AU - Sakaguchi, Masakiyo
AU - Huh, Nam Ho
PY - 2007/11
Y1 - 2007/11
N2 - Transplantation of hepatocytes or hepatocyte-like cells of extrahepatic origin is a promising strategy for treatment of acute and chronic liver failure. We examined possible utility of hepatocyte-like cells induced from bone marrow cells for such a purpose. Clonal cell lines were established from the bone marrow of two different rat strains. One of these cell lines, rBM25/S3 cells, grew rapidly (doubling time, ∼24 hours) without any appreciable changes in cell properties for at least 300 population doubling levels over a period of 300 days, keeping normal diploid karyotype. The cells expressed CD29, CD44, CD49b, CD90, vimentin, and fibronectin but not CD45, indicating that they are of mesenchymal cell origin. When plated on Matrigel with hepatocyte growth factor and fibroblast growth factor-4, the cells efficiently differentiated into hepatocyte-like cells that expressed albumin, cytochrome P450 (CYP) 1A1, CYP1A2, glucose 6-phosphatase, tryptophane-2,3-dioxygenase, tyrosine aminotransferase, hepatocyte nuclear factor (HNF)1α, and HNF4α. Intrasplenic transplantation of the differentiated cells prevented fatal liver failure in 90%-hepatectomized rats. In conclusion, a clonal stem cell line derived from adult rat bone marrow could differentiate into hepatocyte-like cells, and transplantation of the differentiated cells could prevent fatal liver failure in 90%-hepatectomized rats. The present results indicate a promising strategy for treating human fatal liver diseases.
AB - Transplantation of hepatocytes or hepatocyte-like cells of extrahepatic origin is a promising strategy for treatment of acute and chronic liver failure. We examined possible utility of hepatocyte-like cells induced from bone marrow cells for such a purpose. Clonal cell lines were established from the bone marrow of two different rat strains. One of these cell lines, rBM25/S3 cells, grew rapidly (doubling time, ∼24 hours) without any appreciable changes in cell properties for at least 300 population doubling levels over a period of 300 days, keeping normal diploid karyotype. The cells expressed CD29, CD44, CD49b, CD90, vimentin, and fibronectin but not CD45, indicating that they are of mesenchymal cell origin. When plated on Matrigel with hepatocyte growth factor and fibroblast growth factor-4, the cells efficiently differentiated into hepatocyte-like cells that expressed albumin, cytochrome P450 (CYP) 1A1, CYP1A2, glucose 6-phosphatase, tryptophane-2,3-dioxygenase, tyrosine aminotransferase, hepatocyte nuclear factor (HNF)1α, and HNF4α. Intrasplenic transplantation of the differentiated cells prevented fatal liver failure in 90%-hepatectomized rats. In conclusion, a clonal stem cell line derived from adult rat bone marrow could differentiate into hepatocyte-like cells, and transplantation of the differentiated cells could prevent fatal liver failure in 90%-hepatectomized rats. The present results indicate a promising strategy for treating human fatal liver diseases.
KW - Clonal stem cell lines
KW - Hepatocyte-like cells
KW - Intrasplenic transplantation
KW - Mass production
KW - Rat bone marrow
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U2 - 10.1634/stemcells.2007-0078
DO - 10.1634/stemcells.2007-0078
M3 - Article
VL - 25
SP - 2855
EP - 2863
JO - Stem Cells
JF - Stem Cells
SN - 1066-5099
IS - 11
ER -