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TISSUE-SPECIFIC STEM CELLS

Highly Efficient Ex Vivo Expansion of Human Hematopoietic Stem Cells Using Delta1-Fc Chimeric Protein

^aDepartment of Regeneration Medicine for Hematopoiesis, Graduate School of Medicine, University of Tokyo, Tokyo, Japan;
^bDivision of Tissue Engineering, University of Tokyo Hospital, Tokyo, Japan;
^cDepartment of Hematology and Oncology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan;
^dDepartment of Cell Therapy and Transplantation Medicine, University of Tokyo Hospital, Tokyo, Japan;
^eThe Japanese Red Cross Tokyo Blood Center, Tokyo, Japan;
^fDepartment of Perinatal Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan;
^gDepartment of Oral and Maxillofacial Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan;
^hDepartment of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan;
ⁱPharmaceutical Division, Kirin Brewery Co., Ltd., Tokyo, Japan;
^jCorporate R&D and Central Research Laboratory, Asahi Kasei Corporation, Tokyo, Japan

Key Words. AC133 antigen • Hematopoietic stem cells • Notch • Stem cell expansion

Correspondence: Shigeru Chiba, M.D., Ph.D., Department of Cell Therapy and Transplantation Medicine, University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. Telephone: 81-3-5804-6263; Fax: 81-3-5804-6261; e-mail: schiba-tky{at}umin.ac.jp or Seishi Ogawa, M.D., Ph.D., Department of Regeneration Medicine for Hematopoiesis, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. Telephone: 81-3-3815-5411, ext. 35609; Fax: 81-3-5804-6261; e-mail: sogawa-tky{at}umin.ac.jp

Received April 26, 2006; accepted for publication July 11, 2006.
First published online in STEM CELLS EXPRESS   July 20, 2006.



Ex vivo expansion of hematopoietic stem cells (HSCs) has been explored in the fields of stem cell biology, gene therapy, and clinical transplantation. Here, we demonstrate efficient ex vivo expansion of HSCs measured by long-term severe combined immunodeficient (SCID) repopulating cells (SRCs) from human cord blood CD133-sorted cells using a soluble form of Delta1. After a 3-week culture on immobilized Delta1 supplemented with stem cell factor, thrombopoietin, Flt-3 ligand, interleukin (IL)-3, and IL-6/soluble IL-6 receptor chimeric protein (FP6) in a serum- and stromal cell-free condition, we achieved approximately sixfold expansion of SRCs when evaluated by limiting dilution/transplantation assays. The maintenance of full multipotency and self-renewal capacity during culture was confirmed by transplantation to nonobese diabetic/SCID/c^null mice, which showed myeloid, B, T, and natural killer cells as well as CD133⁺CD34⁺ cells, and hematopoietic reconstitution in the secondary recipients. Interestingly, the CD133-sorted cells contained approximately 4.5 times more SRCs than the CD34-sorted cells. The present study provides a promising method to expand HSCs and encourages future trials on clinical transplantation.

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