Open AccessHighly Efficient Ex Vivo Expansion of Human Hematopoietic Stem Cells Using Delta1‐Fc Chimeric Protein
Author(s) -
Suzuki Takahiro,
Yokoyama Yasuhisa,
Kumano Keiki,
Takanashi Minoko,
Kozuma Shiro,
Takato Tsuyoshi,
Nakahata Tatsutoshi,
Nishikawa Mitsuo,
Sakano Seiji,
Kurokawa Mineo,
Ogawa Seishi,
Chiba Shigeru
Publication year - 2006
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1634/stemcells.2006-0258
Subject(s) - biology , stem cell , ex vivo , haematopoiesis , transplantation , cd34 , microbiology and biotechnology , stem cell factor , immunology , hematopoietic stem cell , stromal cell , progenitor cell , cord blood , cancer research , in vivo , medicine , genetics
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/γc 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.