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Prepublished online as a Blood First Edition Paper on December 12, 2002; DOI 10.1182/blood-2002-09-2782.
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Blood, 15 April 2003, Vol. 101, No. 8, pp. 2924-2931
PLENARY PAPER
SCID-repopulating cell activity of human cord blood-derived
CD34 cells assured by intra-bone marrow
injection
Jianfeng Wang,
Takafumi Kimura,
Rumiko Asada,
Sachio Harada,
Shouhei Yokota,
Yoshio Kawamoto,
Yoshihiro Fujimura,
Takashi Tsuji,
Susumu Ikehara, and
Yoshiaki Sonoda
From the Department of Hygiene, the Department of
Digestive Surgery, and the Third Department of Internal Medicine, Kyoto
Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyoku,
Kyoto; the Department of Blood Transfusion Medicine, Nara Medical
University, Shijocho, Kashihara, Nara; the Department of Industrial
Science and Technology, Tokyo University of Science, Yamazaki, Noda,
Chiba; and the First Department of Pathology, Transplantation
Center, Kansai Medical University, Fumizonocho, Moriguchi, Osaka,
Japan.
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.
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