Isolation of a bone marrow-derived stem cell line with high proliferation potential and its application for preventing acute fatal liver failure

Masahiro Miyazaki, Marhaen Hardjo, Takuro Masaka, Koji Tomiyama, Naila Mahmut, Reinhold J. Medina, Aya Niida, Hiroyuki Sonegawa, Gang Du, Rong Yong, Mikiro Takaishi, Masakiyo Sakaguchi, Nam Ho Huh

Research output: Contribution to journalArticle

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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 languageEnglish
Pages (from-to)2855-2863
Number of pages9
JournalStem Cells
Volume25
Issue number11
DOIs
Publication statusPublished - Nov 2007

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Acute Liver Failure
Stem Cells
Bone Marrow
Cell Line
Hepatocytes
Cell Transplantation
Liver Failure
Fibroblast Growth Factor 4
Integrin alpha2beta1
Hepatocyte Nuclear Factor 1
Tyrosine Transaminase
Dioxygenases
Cytochrome P-450 CYP1A2
Glucose-6-Phosphatase
End Stage Liver Disease
Hepatocyte Growth Factor
Vimentin
Diploidy
Karyotype
Fibronectins

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 journalArticle

Miyazaki, M, Hardjo, M, Masaka, T, Tomiyama, K, Mahmut, N, Medina, RJ, Niida, A, Sonegawa, H, Du, G, Yong, R, Takaishi, M, Sakaguchi, M & Huh, NH 2007, 'Isolation of a bone marrow-derived stem cell line with high proliferation potential and its application for preventing acute fatal liver failure', Stem Cells, vol. 25, no. 11, pp. 2855-2863. https://doi.org/10.1634/stemcells.2007-0078
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. / Isolation of a bone marrow-derived stem cell line with high proliferation potential and its application for preventing acute fatal liver failure. In: Stem Cells. 2007 ; Vol. 25, No. 11. pp. 2855-2863.
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AU - Mahmut, Naila

AU - Medina, Reinhold J.

AU - Niida, Aya

AU - Sonegawa, Hiroyuki

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AU - Takaishi, Mikiro

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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.

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