Clonal analysis of hematopoiesis-supporting activity of human mesenchymal stem cells in association with Jagged1 expression and osteogenic potential.
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.
Fujita
Satoshi
S
Department of Reparative Materials, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 615-8211, Japan.
Toguchida
Junya
J
Morita
Yutaka
Y
Iwata
Hiroo
H
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
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