Extensive Studies on Perfusion Method Plus Intra-Bone Marrow-Bone Marrow Transplantation Using Cynomolgus Monkeys

Muneo Inaba^a^,c^,d^,e, Yasushi Adachi^c^,d^,e, Hiroko Hisha^c^,d^,e, Naoki Hosaka^a^,c^,d^,e, Masahiko Maki^a, Yusuke Ueda^a^,b, Yasushi Koike^a, Takeshi Miyake^a, Junichi Fukui^a, Yunze Cui^a^,f, Hiromi Mukaide^a, Naoko Koike^a, Mariko Omae^a, Tomomi Mizokami^a, Akio Shigematsu^a, Yutaku Sakaguchi^a, Masanobu Tsuda^a, Satoshi Okazaki^a, Xiaoli Wang^a, Qing Li^a, Akihisa Nishida^a, Yugo Ando^a, Kequan Guo^a, Changye Song^a, Wenhao Cui^a, Wei Feng^a, Junko Katou^a, Katuyuki Sado^f, Shuji Nakamura^f, Susumu Ikehara^a^,c^,d^,e

^aFirst Department of Pathology,
^bDepartment of Orthopedic Surgery,
^cTransplantation Center,
^dRegeneration Research Center for Intractable Diseases,
^eCenter for Cancer Therapy, Kansai Medical University, Osaka, Japan;
^fJIMRO Co., Ltd., Takasaki, Gunma, Japan

Key Words. Perfusion method • Cynomolgus monkey • Stromal cell • Intra-bone marrow-bone marrow transplantation Colony-forming unit in culture

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

Received on March 13, 2007; accepted for publication on April 27, 2007.

First published online in STEM CELLS EXPRESS May 10, 2007.

The collection of bone marrow cells (BMCs) using a perfusionmethod has been advantageous not only because of the low contaminationof BMCs with T cells from the peripheral blood but also theenrichment of stromal cells, which support hemopoiesis. Beforethe application of this new method to humans, its safety neededto be confirmed using cynomolgus monkeys. We therefore performedthe perfusion method on more than 100 cynomolgus monkeys usingthe long bones (such as the humerus and femur) and also theiliac bones (for human application); in the more than 150 trialsto date, there have been no accidental deaths. Furthermore,the technical safety of a new method for the intra-bone marrow(IBM) injection of BMCs (termed IBM-bone marrow transplantation)has also been confirmed using 30 monkeys.

Disclosure of potential conflicts of interest is found at theend of this article.

TRANSLATIONAL AND CLINICAL RESEARCH

Extensive Studies on Perfusion Method Plus Intra-Bone Marrow-Bone Marrow Transplantation Using Cynomolgus Monkeys