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Molecular and Cellular Biology, June 2005, p. 5183-5195, Vol. 25, No. 12
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.12.5183-5195.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Combination of hTERT and bmi-1, E6, or E7 Induces Prolongation of the Life Span of Bone Marrow Stromal Cells from an Elderly Donor without Affecting Their Neurogenic Potential

Taisuke Mori,^1,2,3 Tohru Kiyono,³ Hideaki Imabayashi,^1,4 Yukiji Takeda,^1,2,6 Kohei Tsuchiya,¹ Shunichirou Miyoshi,⁵ Hatsune Makino,¹ Kenji Matsumoto,⁷ Hirohisa Saito,⁷ Satoshi Ogawa,⁵ Michiie Sakamoto,² Jun-Ichi Hata,¹ and Akihiro Umezawa^1*

Department of Reproductive Biology and Pathology, National Research Institute for Child Health and Development, Tokyo, Japan,¹ Department of Pathology, Keio University School of Medicine, Tokyo, Japan,² Virology Division, National Cancer Center Research Institute, Tokyo, Japan,³ Department of Orthopedic Surgery, Keio University School of Medicine, Tokyo, Japan,⁴ Cardiopulmonary Division, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan,⁵ Department of General Medicine and Clinical Investigation, Nara Medical University, Nara, Japan,⁶ Department of Allergy and Immunology, National Research Institute for Child Health and Development, Tokyo, Japan⁷

Received 11 January 2005/ Returned for modification 13 February 2005/ Accepted 14 March 2005

Murine bone marrow stromal cells differentiate not only into mesodermal derivatives, such as osteocytes, chondrocytes, adipocytes, skeletal myocytes, and cardiomyocytes, but also into neuroectodermal cells in vitro. Human bone marrow stromal cells are easy to isolate but difficult to study because of their limited life span. To overcome this problem, we attempted to prolong the life span of bone marrow stromal cells and investigated whether bone marrow stromal cells modified with bmi-1, hTERT, E6, and E7 retained their differentiated capability, or multipotency. In this study, we demonstrated that the life span of bone marrow stromal cells derived from a 91-year-old donor could be extended and that the stromal cells with an extended life span differentiated into neuronal cells in vitro. We examined the neuronally differentiated cells morphologically, physiologically, and biologically and compared the gene profiles of undifferentiated and differentiated cells. The neuronally differentiated cells exhibited characteristics similar to those of midbrain neuronal progenitors. Thus, the results of this study support the possible use of autologous-cell graft systems to treat central nervous system diseases in geriatric patients.

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* Corresponding author. Mailing address: Department of Reproductive Biology and Pathology, National Research Institute for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo 157-8535, Japan. Phone: 81-3-5494-7047. Fax: 81-3-5494-7048. E-mail: umezawa{at}1985.jukuin.keio.ac.jp.

Supplemental material for this article may be found at http://mcb.asm.org/.

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Molecular and Cellular Biology, June 2005, p. 5183-5195, Vol. 25, No. 12
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.12.5183-5195.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

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