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THE STEM CELL NICHE

Analyses of Very Early Hemopoietic Regeneration After Bone Marrow Transplantation: Comparison of Intravenous and Intrabone Marrow Routes

^aFirst Department of Pathology,
^bRegeneration Therapy,
^cRegeneration Research Center for Intractable Diseases, Kansai Medical University, Osaka, Japan;
^dDepartment of Pathology, North Taiping Road Hospital, Beijing, China

Key Words. Intravenous-bone marrow transplantation • Intrabone marrow-bone marrow transplantation • Hemopoietic regeneration Chemotaxis

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: 81-6-6993-949; Fax: 81-6-6994-8283; e-mail: ikehara{at}takii.kmu.ac.jp

Received June 9, 2006; accepted for publication January 3, 2007.
First published online in STEM CELLS EXPRESS   February 22, 2007.



In bone marrow transplantation (BMT), bone marrow cells (BMCs) have traditionally been injected intravenously. However, remarkable advantages of BMT via the intra-bone-marrow (IBM) route (IBM-BMT) over the intravenous route (IV-BMT) have been recently documented by several laboratories. To clarify the mechanisms underlying these advantages, we analyzed the kinetics of hemopoietic regeneration after IBM-BMT or IV-BMT in normal strains of mice. At the site of the direct injection of BMCs, significantly higher numbers of donor-derived cells in total and of c-kit⁺ cells were observed at 2 through 6 days after IBM-BMT. In parallel, significantly higher numbers of colony-forming units in spleen were obtained from the site of BMC injection. During this early period, higher accumulations of both hemopoietic cells and stromal cells were observed at the site of BMC injection by the IBM-BMT route. The production of chemotactic factors, which can promote the migration of a BM stromal cell line, was observed in BMCs obtained from irradiated mice as early as 4 hours after irradiation, and the production lasted for at least 4 days. In contrast, sera collected from the irradiated mice showed no chemotactic activity, indicating that donor BM stromal cells that entered systemic circulation cannot home effectively into recipient bone cavity. These results strongly suggest that the concomitant regeneration of microenvironmental and hemopoietic compartments in the marrow (direct interaction between them at the site of injection) contributes to the advantages of IBM-BMT over IV-BMT.

Disclosure of potential conflicts of interest is found at the end of this article.

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