| Autor: |
Wang, Jianfeng, Kimura, Takafumi, Asada, Rumiko, Harada, Sachio, Yokota, Shouhei, Kawamoto, Yoshio, Fujimura, Yoshihiro, Tsuji, Takashi, Ikehara, Susumu, Sonoda, Yoshiaki |
| Zdroj: |
Blood; April 2003, Vol. 101 Issue: 8 p2924-2931, 8p |
| Abstrakt: |
Precise analysis of human CD34-negative (CD34−) hematopoietic stem cells (HSCs) has been hindered by the lack of a simple and reliable assay system of these rare cells. Here, we successfully identify human cord blood–derived CD34−severe combined immunodeficiency (SCID)– repopulating cells (SRCs) with extensive lymphoid and myeloid repopulating ability using the intra–bone marrow injection (IBMI) technique. Lineage-negative (Lin−) CD34−cells did not show SRC activity by conventional tail-vein injection, possibly due to their low levels of homing receptor expression and poor SDF-1/CXCR4– mediated homing abilities, while they clearly showed a high SRC activity by IBMI. They generated CD34+progenies not only in the injected left tibia but also in other bones following migration. Moreover, they showed slower differentiating and reconstituting kinetics than CD34+cells in vivo. These in vivo–generated CD34+cells showed a distinct SRC activity after secondary transplantation, clearly indicating the long-term human cell repopulating capacity of our identified CD34−SRCs in nonobese diabetic (NOD)/SCID mice. The unveiling of this novel class of primitive human CD34−SRCs by IBMI will provide a new concept of the hierarchy in the human HSC compartment and has important implications for clinical HSC transplantation as well as for basic research of HSC. |
| Databáze: |
Supplemental Index |
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