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THE STEM CELL NICHE

Ex Vivo Culture of Human Cord Blood Hematopoietic Stem/Progenitor Cells Adversely Influences Their Distribution to Other Bone Marrow Compartments After Intra-Bone Marrow Transplantation

^aDepartment of Hematology and Oncology, Mie University Graduate School of Medicine, Mie, Japan;
^bBlood Transfusion Service, Mie University Hospital, Mie, Japan

Key Words. Cord blood • Intra-bone marrow • Transplantation • Migration • In vitro culture

Correspondence: Kohshi Ohishi, M.D., Ph.D., Department of Hematology and Oncology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan. Telephone: 81-59-231-5016; Fax: 81-59-231-5216; e-mail: koishi{at}clin.medic.mie-u.ac.jp; or Naoyuki Katayama, M.D., Ph.D., Department of Hematology and Oncology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan. Telephone: 81-59-231-5016; Fax: 81-59-231-5216; e-mail: n-kata{at}clin.medic.mie-u.ac.jp

Received June 17, 2007; accepted for publication October 22, 2007.
First published online in STEM CELLS EXPRESS   November 1, 2007.



Intra-bone marrow injection is a novel strategy for hematopoietic stem cell transplantation. Here, we investigated whether ex vivo culture of cord blood hematopoietic stem/progenitor cells influences their reconstitution in bone marrow after intra-bone marrow transplantation. Freshly isolated AC133⁺ cells or cells derived from AC133⁺ cells cultured with cytokines (stem cell factor, flt-3 ligand, and thrombopoietin) for 5 days were injected into the bone marrow of the left tibia in irradiated NOD/SCID mice. In the bone marrow of the injected left tibia, the engraftment levels of human CD45⁺ cells at 6 weeks after transplantation did not differ considerably between transplantation of noncultured and cytokine-cultured cells. However, the migration and distribution of transplanted cells to the bone marrow of other, noninjected bones were extremely reduced for cytokine-treated cells compared with noncultured cells. Similar findings were observed for engraftment of CD34⁺ cells. Administration of granulocyte colony-stimulating factor to mice after transplantation induced the migration of cytokine-cultured cells to the bone marrow of previously aspirated bone but not to other intact bones. These data suggest that ex vivo manipulation of hematopoietic progenitor/stem cells significantly affects their migration properties to other bone marrow compartments after intra-bone marrow transplantation. Our data raise a caution for future clinical applications of the intra-bone marrow transplantation method using ex vivo-manipulated hematopoietic stem cells.

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