title: Reconstitution activity of hypoxic cultured human cord blood CD34-positive cells in NOG mice.
abstract: Hematopoietic stem cells (HSCs) reside in hypoxic areas of the bone marrow. However, the role of hypoxia in the maintenance of HSCs has not been fully characterized. We performed xenotransplantation of human cord blood cells cultured in hypoxic or normoxic conditions into adult NOD/SCID/IL-2Rgamma(null) (NOG) mice. Hypoxic culture (1% O(2)) for 6 days efficiently supported the maintenance of HSCs, although cell proliferation was suppressed compared to the normoxic culture. In contrast, hypoxia did not affect in vitro colony-forming ability. Upregulation of a cell cycle inhibitor, p21, was observed in hypoxic culture. Immunohistochemical analysis of recipient bone marrow revealed that engrafted CD34(+)CD38(-) cord blood HSCs were hypoxic. Taken together, these results demonstrate the significance of hypoxia in the maintenance of quiescent human cord blood HSCs.
authors.affiliation: Department of Cell Differentiation, The Sakaguchi Laboratory of Developmental Biology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Haruko
authors.initials: H
authors.lastname: Shima
authors.forename: Keiyo
authors.initials: K
authors.lastname: Takubo
authors.forename: Hiroko
authors.initials: H
authors.lastname: Iwasaki
authors.forename: Hiroki
authors.initials: H
authors.lastname: Yoshihara
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Gomei
authors.forename: Kentaro
authors.initials: K
authors.lastname: Hosokawa
authors.forename: Fumio
authors.initials: F
authors.lastname: Arai
authors.forename: Takao
authors.initials: T
authors.lastname: Takahashi
authors.forename: Toshio
authors.initials: T
authors.lastname: Suda
mesh_terms: D000693:Anaerobiosis; D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D002478:Cells, Cultured; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D005312:Fetal Blood / Q000166:cytology* / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology*; D006801:Humans; D051379:Mice; D008817:Mice, Mutant Strains; D014183:Transplantation, Heterologous; D015854:Up-Regulation
chemical_list: D018952:Antigens, CD34; D050759:Cyclin-Dependent Kinase Inhibitor p21