title: Early osteoinductive human bone marrow mesenchymal stromal/stem cells support an enhanced hematopoietic cell expansion with altered chemotaxis- and adhesion-related gene expression profiles.
abstract: Bone marrow (BM) microenvironment has a crucial role in supporting hematopoiesis. Here, by using a microarray analysis, we demonstrate that human BM mesenchymal stromal/stem cells (MSCs) in an early osteoinductive stage (e-MSCs) are characterized by unique hematopoiesis-associated gene expression with an enhanced hematopoiesis-supportive ability. In comparison to BM-MSCs without osteoinductive treatment, gene expression in e-MSCs was significantly altered in terms of their cell adhesion- and chemotaxis-related profiles, as identified with Gene Ontology and Gene Set Enrichment Analysis. Noteworthy, expression of the hematopoiesis-associated molecules CXCL12 and vascular cell adhesion molecule 1 was remarkably decreased in e-MSCs. e-MSCs supported an enhanced expansion of CD34(+) hematopoietic stem and progenitor cells, and generation of myeloid lineage cells in vitro. In addition, short-term osteoinductive treatment favored in vivo hematopoietic recovery in lethally irradiated mice that underwent BM transplantation. e-MSCs exhibited the absence of decreased stemness-associated gene expression, increased osteogenesis-associated gene expression, and apparent mineralization, thus maintaining the ability to differentiate into adipogenic cells. Our findings demonstrate the unique biological characteristics of e-MSCs as hematopoiesis-regulatory stromal cells at differentiation stage between MSCs and osteoprogenitor cells and have significant implications in developing new strategy for using pharmacological osteoinductive treatment to support hematopoiesis in hematopoietic stem and progenitor cell transplantation.
authors.affiliation: Department of Hematology/Oncology, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan; Department of Transfusion Medicine and Cell Therapy, Kyoto University Hospital, Kyoto 606-8507, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Sugino
authors.affiliation: Department of Transfusion Medicine and Cell Therapy, Kyoto University Hospital, Kyoto 606-8507, Japan. Electronic address: ym58f5@kuhp.kyoto-u.ac.jp.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Miura
authors.affiliation: Department of Transfusion Medicine and Cell Therapy, Kyoto University Hospital, Kyoto 606-8507, Japan.
authors.forename: Hisayuki
authors.initials: H
authors.lastname: Yao
authors.affiliation: Department of Transfusion Medicine and Cell Therapy, Kyoto University Hospital, Kyoto 606-8507, Japan; Division of Gastroenterology and Hematology, Shiga University of Medical Science, Shiga 520-2192, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Iwasa
authors.affiliation: Department of Transfusion Medicine and Cell Therapy, Kyoto University Hospital, Kyoto 606-8507, Japan; Division of Gastroenterology and Hematology, Shiga University of Medical Science, Shiga 520-2192, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Fujishiro
authors.affiliation: Department of Hematology/Oncology, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan; Department of Transfusion Medicine and Cell Therapy, Kyoto University Hospital, Kyoto 606-8507, Japan.
authors.forename: Sumie
authors.initials: S
authors.lastname: Fujii
authors.affiliation: Department of Transfusion Medicine and Cell Therapy, Kyoto University Hospital, Kyoto 606-8507, Japan.
authors.forename: Hideyo
authors.initials: H
authors.lastname: Hirai
authors.affiliation: Department of Hematology/Oncology, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.
authors.forename: Akifumi
authors.initials: A
authors.lastname: Takaori-Kondo
authors.affiliation: Department of Hematology and Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima 734-8553, Japan.
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Ichinohe
authors.affiliation: Department of Transfusion Medicine and Cell Therapy, Kyoto University Hospital, Kyoto 606-8507, Japan.
authors.forename: Taira
authors.initials: T
authors.lastname: Maekawa
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D002633:Chemotaxis / Q000502:physiology; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000502:physiology; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010006:Osteoblasts / Q000166:cytology* / Q000502:physiology*; D010012:Osteogenesis / Q000502:physiology*
keywords: Bone marrow mesenchymal stromal/stem cells; CXCL12; Hematopoiesis