Analyses of Very Early Hemopoietic Regeneration After Bone Marrow Transplantation: Comparison Between Intravenous and Intra-Bone Marrow Routes

¹ First Department of Pathology, Kansai Medical University, Osaka, Japan; Department of Pathology, North Taiping Road Hospital, Beijing, China
² First Department of Pathology, Kansai Medical University, Osaka, Japan; Regeneration Therapy, Kansai Medical University, Osaka, Japan; Regeneration Research Center for Intractable Diseases, Kansai Medical University, Osaka, Japan
³ First Department of Pathology, Kansai Medical University, Osaka, Japan

^* To whom correspondence should be addressed. E-mail: ikehara{at}takii.kmu.ac.jp.

	Abstract

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 (IV) 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 unit in spleen (CFU-S) 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 at least up to 4 days. In contrast, sera collected from the irradiated mice did not show any 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.

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