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 Jagged1, 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.
Document Type: Research Article
Publication date: 2008-10-01
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