title: Clonal analysis of hematopoiesis-supporting activity of human mesenchymal stem cells in association with Jagged1 expression and osteogenic potential.
abstract: Human mesenchymal stem cells (hMSCs) are promising feeder cells for expanding hematopoietic stem cells (HSCs), but their potential is heterogeneous. We examined the hematopoiesis-supporting activity of hMSC at the clonal level in relation to the osteogenic potential and gene expression. Hematopoiesis-supporting activities of stably immortalized clonal hMSC lines were evaluated by the expansion of CD34+CD38- cells after 7-day coculture with human cord blood-derived CD34+ cells. Six of 16 clones expanded the numbers of CD34+CD38- cells >500-fold. These hematopoiesis-supportive clones also showed high gene expression of Jaggedl, a Notch ligand, as well as high potential to deposit calcium after osteogenic induction. Thus, osteogenic hMSC clones may provide proper microenvironments for HSC expansion, ultimately conveying self-renewal signals to HSCs via the Notch pathway. However, they lost hematopoiesis-supporting activity after osteogenic differentiation. The hematopoiesis-supportive clones are potentially useful for hematopoietic microenvironment studies and as components of a coculture system for expansion of HSCs, free from contamination by xenogeneic pathogens.
authors.affiliation: Department of Reparative Materials, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 615-8211, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Fujita
authors.forename: Junya
authors.initials: J
authors.lastname: Toguchida
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Morita
authors.forename: Hiroo
authors.initials: H
authors.lastname: Iwata
mesh_terms: D018952:Antigens, CD34 / Q000235:genetics / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D002999:Clone Cells; D018920:Coculture Techniques; D015870:Gene Expression / Q000502:physiology; D020869:Gene Expression Profiling; D006410:Hematopoiesis / Q000235:genetics* / Q000502:physiology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D000072100:Jagged-1 Protein; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000502:physiology*; D010012:Osteogenesis / Q000235:genetics* / Q000502:physiology; D000072099:Serrate-Jagged Proteins
chemical_list: D018952:Antigens, CD34; D002135:Calcium-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; C000606273:JAG1 protein, human; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D000072099:Serrate-Jagged Proteins; D002118:Calcium