Multipotent cells from the human third molar: feasibility of cell-based therapy for liver disease

Multipotent cells from the human third molar: feasibility of cell-based therapy for liver disease
18 Dec 2007
Received June 4, 2007; accepted in revised form September 17, 2007
To cite this article: Etsuko Ikeda, Kiyohito Yagi, Midori Kojima, Takahiro Yagyuu, Akira Ohshima, Satoshi Sobajima, Mika Tadokoro, Yoshihiro Katsube, Katsuhiro Isoda, Masuo Kondoh, Masaya Kawase, Masahiro J Go, Hisashi Adachi, Yukiharu Yokota, Tadaaki Kirita, Hajime Ohgushi (2007)
Multipotent cells from the human third molar: feasibility of cell-based therapy for liver disease
doi:10.1111/j.1432-0436.2007.00245.x
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Etsuko Ikeda11Research Institute for Cell Engineering (RICE), National Institute of Advanced Industrial Science and Technology (AIST), 3-11-46 Nakoji, Amagasaki, Hyogo 661-0974, Japan.
Tel: +81 6 6494 7807
Fax: +81 6 6494 7861* E-mail: etu-ikeda@aist.go.jp ? Kiyohito Yagi22Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 565-0871, Japan* ? Midori Kojima22Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 565-0871, Japan ? Takahiro Yagyuu33Department of Oral and Maxillofacial Surgery, Nara Medical University, Kashihara, Nara 634-8521, Japan ? Akira Ohshima11Research Institute for Cell Engineering (RICE), National Institute of Advanced Industrial Science and Technology (AIST), 3-11-46 Nakoji, Amagasaki, Hyogo 661-0974, Japan.
Tel: +81 6 6494 7807
Fax: +81 6 6494 7861 ? Satoshi Sobajima11Research Institute for Cell Engineering (RICE), National Institute of Advanced Industrial Science and Technology (AIST), 3-11-46 Nakoji, Amagasaki, Hyogo 661-0974, Japan.
Tel: +81 6 6494 7807
Fax: +81 6 6494 7861 ? Mika Tadokoro11Research Institute for Cell Engineering (RICE), National Institute of Advanced Industrial Science and Technology (AIST), 3-11-46 Nakoji, Amagasaki, Hyogo 661-0974, Japan.
Tel: +81 6 6494 7807
Fax: +81 6 6494 7861 ? Yoshihiro Katsube11Research Institute for Cell Engineering (RICE), National Institute of Advanced Industrial Science and Technology (AIST), 3-11-46 Nakoji, Amagasaki, Hyogo 661-0974, Japan.
Tel: +81 6 6494 7807
Fax: +81 6 6494 7861 ? Katsuhiro Isoda22Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 565-0871, Japan ? Masuo Kondoh22Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 565-0871, Japan ? Masaya Kawase22Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 565-0871, Japan ? Masahiro J Go11Research Institute for Cell Engineering (RICE), National Institute of Advanced Industrial Science and Technology (AIST), 3-11-46 Nakoji, Amagasaki, Hyogo 661-0974, Japan.
Tel: +81 6 6494 7807
Fax: +81 6 6494 7861 ? Hisashi Adachi11Research Institute for Cell Engineering (RICE), National Institute of Advanced Industrial Science and Technology (AIST), 3-11-46 Nakoji, Amagasaki, Hyogo 661-0974, Japan.
Tel: +81 6 6494 7807
Fax: +81 6 6494 7861 ? Yukiharu Yokota11Research Institute for Cell Engineering (RICE), National Institute of Advanced Industrial Science and Technology (AIST), 3-11-46 Nakoji, Amagasaki, Hyogo 661-0974, Japan.
Tel: +81 6 6494 7807
Fax: +81 6 6494 7861 ? Tadaaki Kirita33Department of Oral and Maxillofacial Surgery, Nara Medical University, Kashihara, Nara 634-8521, Japan ? Hajime Ohgushi11Research Institute for Cell Engineering (RICE), National Institute of Advanced Industrial Science and Technology (AIST), 3-11-46 Nakoji, Amagasaki, Hyogo 661-0974, Japan.
Tel: +81 6 6494 7807
Fax: +81 6 6494 7861

E-mail: etu-ikeda@aist.go.jp
*Both authors are first authors.

Abstract
Abstract Adult stem cells have been reported to exist in various tissues. The isolation of high-quality human stem cells that can be used for regeneration of fatal deseases from accessible resources is an important advance in stem cell research. In the present study, we identified a novel stem cell, which we named tooth germ progenitor cells (TGPCs), from discarded third molar, commonly called as wisdom teeth. We demonstrated the characterization and distinctiveness of the TGPCs, and found that TGPCs showed high proliferation activity and capability to differentiate in vitro into cells of three germ layers including osteoblasts, neural cells, and hepatocytes. TGPCs were examined by the transplantation into a carbon tetrachloride (CCl4)-treated liver injured rat to determine whether this novel cell source might be useful for cell-based therapy to treat liver diseases. The successful engraftment of the TGPCs was demonstrated by PKH26 fluorescence in the recipient's rat as to liver at 4 weeks after transplantation. The TGPCs prevented the progression of liver fibrosis in the liver of CCl4-treated rats and contributed to the restoration of liver function, as assessed by the measurement of hepatic serum markers aspartate aminotransferase and alanine aminotransferase. Furthermore, the liver functions, observed by the levels of serum bilirubin and albumin, appeared to be improved following transplantation of TGPCs. These findings suggest that multipotent TGPCs are one of the candidates for cell-based therapy to treat liver diseases and offer unprecedented opportunities for developing therapies in treating tissue repair and regeneration.

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