title: Prospectively Isolated Human Bone Marrow Cell-Derived MSCs Support Primitive Human CD34-Negative Hematopoietic Stem Cells.
abstract: Hematopoietic stem cells (HSCs) are maintained in a specialized bone marrow (BM) niche, which consists of osteoblasts, endothelial cells, and a variety of mesenchymal stem/stromal cells (MSCs). However, precisely what types of MSCs support human HSCs in the BM remain to be elucidated because of their heterogeneity. In this study, we succeeded in prospectively isolating/establishing three types of MSCs from human BM-derived lineage- and CD45-negative cells, according to their cell surface expression of CD271 and stage-specific embryonic antigen (SSEA)-4. Among them, the MSCs established from the Lineage(-) CD45(-) CD271(+) SSEA-4(+) fraction (DP MSC) could differentiate into osteoblasts and chondrocytes, but they lacked adipogenic differentiation potential. The DP MSCs expressed significantly higher levels of well-characterized HSC-supportive genes, including IGF-2, Wnt3a, Jagged1, TGFβ3, nestin, CXCL12, and Foxc1, compared with other MSCs. Interestingly, these osteo-chondrogenic DP MSCs possessed the ability to support cord blood-derived primitive human CD34-negative severe combined immunodeficiency-repopulating cells. The HSC-supportive actions of DP MSCs were partially carried out by soluble factors, including IGF-2, Wnt3a, and Jagged1. Moreover, contact between DP MSCs and CD34-positive (CD34(+) ) as well as CD34-negative (CD34(-) ) HSCs was important for the support/maintenance of the CD34(+/-) HSCs in vitro. These data suggest that DP MSCs might play an important role in the maintenance of human primitive HSCs in the BM niche. Therefore, the establishment of DP MSCs provides a new tool for the elucidation of the human HSC/niche interaction in vitro as well as in vivo.
authors.affiliation: Department of Stem Cell Biology and Regenerative Medicine, Graduate School of Medical Science, Hirakata, Osaka, Japan.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Matsuoka
authors.forename: Ryusuke
authors.initials: R
authors.lastname: Nakatsuka
authors.forename: Keisuke
authors.initials: K
authors.lastname: Sumide
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawamura
authors.forename: Masaya
authors.initials: M
authors.lastname: Takahashi
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Fujioka
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Uemura
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Asano
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Sasaki
authors.forename: Masami
authors.initials: M
authors.lastname: Inoue
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Ogawa
authors.forename: Takayuki
authors.initials: T
authors.lastname: Takahashi
authors.forename: Masayuki
authors.initials: M
authors.lastname: Hino
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Sonoda
mesh_terms: D000068816:Adapalene / Q000378:metabolism; D050156:Adipogenesis / Q000235:genetics; D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism; D049109:Cell Proliferation; D002469:Cell Separation / Q000379:methods*; D020219:Chondrogenesis / Q000235:genetics; D003114:Colony-Forming Units Assay; D005260:Female; D005312:Fetal Blood / Q000166:cytology; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D010012:Osteogenesis / Q000235:genetics; D055746:Stage-Specific Embryonic Antigens / Q000378:metabolism
chemical_list: D018952:Antigens, CD34; D015415:Biomarkers; D055746:Stage-Specific Embryonic Antigens; C066584:stage-specific embryonic antigen-4; D000068816:Adapalene
keywords: CD271; CD34-negative; Hematopoietic stem cell; Mesenchymal stem/stromal cells; Niche; SSEA-4