Adult Stem Cells & Cancer Laboratory

Telephone: (518) 474-0547
Fax: (518) 473-2900
ssell@ordwayresearch.org

Research Focus

The work of Dr. Sell and his laboratory is directed at four key areas of adult stem sells in cancer and aging.

1. The role of bone marrow and tissue stem cells in repair of liver injury and as the cells of origin of liver cancer are being examined in different models of liver toxicity and carcinogenesis in rats and mice. Different injury and carcinogenesis models induce different patterns of cellular response indicating that cells at different stages of stem cell to hepatocyte differentiation may give rise to liver cancer. The possibility that bone marrow stem cells may be cells of origin of liver cancer is being tested using bone marrow transplantation.

2. The hypothesis that aging is determined by the number or properties of stem cells in the bone marrow is being tested by transplanting bone marrow cells from early aging mice to normal mice and by transplanting normal bone marrow to early aging mice.

3. The plasticity of a fetal mouse fibroblast cell line to transdifferentiate into other tissues and to be accepted across histocompatibility barriers is being tested in rat and mouse models of injury and repair. Our preliminary data indicate that the tissue niche may determine if these cells demonstrate immune privileged and differentiation into different cell types upon transplantation.

4. The mechanisms of the interplay of the major risk factors for human liver cancer were examined in mouse models of hepatocarcinogenesis and the critical role of glutationine-s-transferase in metabolism of aflatoxin was identified as the most important factor for susceptibility to aflatoxin carcinogenesis. We are now deriving a GST knockout mouse line to examine further this critical pathway.

5. Finally the contribution of bone marrow stem cells to breast cancer is being tested using transplantation of bone marrow from male donors with strong oncogenes under the control of breast specific promoters to normal female mice.

Selected Publications
www.pubmed.com

Shupe T, Sell S . Low hepatic glutathione-S-transferase and increased hepatic DNA adduction contribute to tumorigenicity of aflatoxin B1 in newborn and partially hepatectomized mice. Toxicology Lett., 148:1-9, 2004.

Sell S . Mouse models to study the interaction of risk factors for human liver cancer. Cancer Res.  63:7553-7562, 2003.

Sell S . Stem cell origin of cancer and differentiation therapy. Crit. Rev. Oncology and Hematology, 52:1-28, 2004.

Zhang M, Joseph B, Gupta S, Guest I, Sell S . Son K-H, Koch KS , Leffert H. Embryonic mouse STO cell-derived xenografts express hepatocyte functions in livers of non-immunosuppressed adult rats. Stem Cells 23: 186-199, 2005

Sell S . Cancer Stem Cells and Differentiation Therapy. Tumor Biology. 27:59-70, 2006

Crawford DR , Ostrowski S, Vakharia D, Ilic Z, Sell S . Separate origins of hepatitis B virus-negative foci and hepatocellular carcinomas in HBsAg transgenic ( alb/psx ) mice. Am J. Pathology, in press.

Koch KS, Son K-W, Maehr R, Pellicciotta I, Ploegh, HL, Sanetti M, Sell S, Leffert HL. Immune-privileged embryonic Swiss mouse STO and STO cell-derived progenitor cells: MHC and cell differentiation antigen expression resemble those of human embryonic stem cell lines. Immunology. in press.

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