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First published online August 18, 2005
Stem Cells Vol. 24 No. 2 February 2006, pp. 399 -405
doi:10.1634/stemcells.2005-0068; www.StemCells.com
© 2006 AlphaMed Press

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TRANSLATIONAL AND CLINICAL RESEARCH

Treatment of Senile Osteoporosis in SAMP6 Mice by Intra–Bone Marrow Injection of Allogeneic Bone Marrow Cells

Keizo Takada, Muneo Inaba, Naoya Ichioka, Yusuke Ueda, Mitsuru Taira, Susumu Baba, Tomomi Mizokami, Xiaoli Wang, Hiroko Hisha, Hirokazu Iida, Susumu Ikehara

First Department of Pathology, Department of Orthopedic Surgery, Department of Obstetrics and Gynecology, Transplantation Center, Kansai Medical University, Moriguchi City, Osaka, Japan

Key Words. Senescence-accelerated mouse prone 6 mice • Osteoporosis • Intra–bone marrow • Bone marrow transplantation • Bone mineral density • Deoxypyridinoline

Correspondence: Susumu Ikehara, M.D., Ph.D., First Department of Pathology, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi City, Osaka 570-8506, Japan. Telephone: 81-6-6993-9429; Fax: 81-6-6994-8283; e-mail: ikehara{at}takii.kmu.ac.jp

A substrain of the senescence-accelerated mouse, SAMP6 (senescence-accelerated mouse prone 6), spontaneously develops osteoporosis early in life. Therefore, this strain is a useful animal model for developing new strategies for the treatment of osteoporosis in humans. We succeeded in treating osteoporosis in SAMP6 mice after the onset of this disease, using a newly developed method of bone marrow transplantation (BMT): Allogeneic bone marrow cells obtained from normal mouse strains were directly injected into the bone marrow cavity of irradiated SAMP6 mice (intra–bone marrow BMT [IBM-BMT]). After the treatment with IBM-BMT, hematolymphoid cells were completely reconstituted by donor-derived cells, and bone marrow stromal cells were also found to be of donor origin. The treated SAMP6 mice showed histologically-normal trabecular bone. In addition, bone mineral density and urinary deoxypiridinoline, a hallmark of bone destruction, were normalized. When the message levels of cytokines (tumor necrosis factor {alpha}, interleukin-6 [IL-6], IL-11, and receptor activator of nuclear factor–{kappa} B ligand [RANKL]) were examined, IL-11, RANKL (from bone marrow stromal cells), and IL-6 (from osteoclasts), which regulate bone remodeling, were restored to levels similar to those in normal B6 mice. These findings indicate that not only the hemopoietic system but also the bone marrow microenvironment were normalized after IBM-BMT, resulting in an amelioration of the imbalance between bone absorption and formation.




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