Human Hematopoietic Stem Cells: The Current Understanding and Future Prospects Pleurisy as a novel clinical manifestation associated with human herpesvirus 6 after unrelated cord blood transplantation Case report

(cid:242) (cid:675) . CD34 is a surface glycoprotein that is expressed on early lymphomyeloid hematopoietic stem (cid:246) progenitor cells (cid:674) HSPCs (cid:675) . 2 In fact, immunomagnetically separated CD34 (cid:242) cell populations obtained from BM and peripheral blood (cid:674) PB (cid:675) can form all types of HPC-derived colonies, and achieve long-term (cid:674) LT (cid:675) donor-derived lymphohematopoi-Submitted Based on the recent progress of fluorescence-activated cell sorting technology, murine hematopoietic stem cells（HSCs）can be purified to the single cell level. The immunophenotype of murine HSCs is CD34 c-kit ＋ Sca-1 ＋ Lin － （CD34 KSL）. However, the stem cell nature of primitive human HSCs has not been fully elucidated. The biology of human HSCs is a current topic of interest that has important implications for hematopoietic stem cell transplantation（HSCT）as well as basic research on HSCs. We identified human cord blood（CB）-derived CD34 － SCID-repopulating cells（SRCs）（HSCs）, which seemed to be a counterpart of murine CD34 low／－ KSL cells, using an intra-bone marrow injection（IBMI）method. Our series of studies has elucidated the stem cell nature of these CD34 － HSCs as well as CD34 ＋ HSCs. The purpose of this review is to provide an update of the concept of the immunophenotype and functional characteristics of human primitive CD34 ＋／－ HSCs. In addition, the significance of the application of the IBMI technique in clinical HSCT is also discussed. Recent advances in the understanding of the biological nature of human HSCs may make it possible to fully characterize the most primitive class of human HSCs, and thereby clarify the human HSC hierarchy, in the near future. We report the case of a 45-year-old male patient who developed human herpesvirus 6 (HHV6)-associated pleurisy after an unrelated cord blood transplantation (CBT) for acute lymphoblastic leukemia. A large amount of pleural effusion accompanied by interstitial pneumonitis was noted on the right side on day 37 post-transplantation. A real-time quantitative PCR (RQ-PCR) assay revealed that the HHV6 viral load was substantially higher in the pleural effusion than in the peripheral blood plasma at the onset of pleurisy, with 2.2 × 10 2 and 7.9 × 10 3 copies of HHV6 DNA/mL in the peripheral blood plasma and the supernatant of the pleural effusion, respectively. Moreover, HHV6 DNA was still detected in the pleural effusion after antiviral therapy. Therefore, the pleural cavity may have been the primary site of HHV6 replication in the present case. To our knowledge, the present study is the first detailed report of adult HHV6-associated pleurisy after CBT. HHV6-associated pleurisy should be considered a potential complication when pleural effusion of unknown cause is encountered after CBT, even in the absence of HHV6 DNA in the peripheral blood. (Journal of Hematopoietic Cell Transplantation 3(2): 59-63, 2014. ) of purified Lin (cid:693) CD34 (cid:242) CD38 (cid:693) cells in preimmune fetal sheep and homozygous bg.bg (cid:246) nu.nu (cid:246) xid.xid (cid:674) bnx (cid:675) mice. These studies indicate the possibility that the BM-derived CD34 (cid:242) cell (cid:693) (cid:693) SRCs 39,40 (cid:242) These findings suggest that the expression patterns of CD34 and MPL receptors defines three classes of human CB-derived HSCs, including IT- and LT-repopulating HSCs, and provide a new concept that CD34 (cid:693) MPL (cid:693) SRCs reside at the apex of the human HSC hierarchy (cid:674) Matsuoka and Sonoda, manuscript submitted (cid:675)