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Title: Directed differentiation of hematopoietic precursors and functional osteoclasts from human ES and iPS cells
Authors: Grigoriadis, AE
Kennedy, M
Bozec, A
Brunton, F
Stenbeck, G
Park, IH
Wagner, EF
Keller, GM
Keywords: Embryonic stem-cells;Human blastocysts;In-vitro;Bone;Lines;Osteopetrosis;Progenitors;Communication;Pluripotency;Osteoporosis
Issue Date: 2010
Publisher: American Society of Hematology
Citation: Blood 115(14): 2769 - 2776, Apr 2010
Abstract: The directed differentiation of human pluripotent stem cells offers the unique opportunity to generate a broad spectrum of human cell types and tissues for transplantation, drug discovery, and studying disease mechanisms. Here, we report the stepwise generation of bone-resorbing osteoclasts from human embryonic and induced pluripotent stem cells. Generation of a primitive streak-like population in embryoid bodies, followed by specification to hematopoiesis and myelopoiesis by vascular endothelial growth factor and hematopoietic cytokines in serum-free media, yielded a precursor population enriched for cells expressing the monocyte-macrophage lineage markers CD14, CD18, CD11b, and CD115. When plated in monolayer culture in the presence of macrophage colony-stimulating factor and receptor activator of nuclear factor-kappa B ligand (RANKL), these precursors formed large, multinucleated osteoclasts that expressed tartrate-resistant acid phosphatase and were capable of resorption. No tartrate-resistant acid phosphatase-positive multinucleated cells or resorption pits were observed in the absence of RANKL. Molecular analyses confirmed the expression of the osteoclast marker genes NFATc1, cathepsin K, and calcitonin receptor in a RANKL-dependent manner, and confocal microscopy demonstrated the coexpression of the alpha v beta 3 integrin, cathepsin K and F-actin rings characteristic of active osteoclasts. Generating hematopoietic and osteoclast populations from human embryonic and induced pluripotent stem cells will be invaluable for understanding embryonic bone development and postnatal bone disease. (Blood. 2010; 115(14): 2769-2776)
Description: This article has been made available through the Brunel Open Access Publishing Fund and is available from the specified link - 2010 by The American Society of Hematology
ISSN: 0006-4971
Appears in Collections:Biological Sciences
Dept of Life Sciences Research Papers

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