NDLI: OP9 Stroma Augments Survival of Hematopoietic Precursors and Progenitors During Hematopoietic Differentiation from Human Embryonic Stem Cells

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OP9 Stroma Augments Survival of Hematopoietic Precursors and Progenitors During Hematopoietic Differentiation from Human Embryonic Stem Cells

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Ji, Junfeng Vijayaragavan, Kausalia Bosse, Marc Menendez, Pablo Weisel, Katja Bhatia, Mickie
Description	Country affiliation: Canada Author Affiliation: Ji J ( Faculty of Health Sciences, Stem Cell and Cancer Research Institute, McMaster University, Hamilton, Ontario, Canada.)
Abstract	The cellular mechanism and target cell affected by stromal microenvironments in augmenting hematopoietic specification from pluripotent human embryonic stem cells (hESCs) has yet to be evaluated. Here, in contrast to aorta-gonad-mesonephros-derived S62 stromal cells, OP9 cells inhibit apoptosis and also augment the proliferation of hemogenic precursors prospectively isolated from human embryoid bodies. In addition, OP9 stroma supported cells within the primitive hematopoietic compartment by inhibiting apoptosis of $CD45^{+}CD34^{+}$ cells committed to the hematopoietic lineage, but have no effect on more mature blood $(CD45^{+}CD34^{−})$ cells. Inability of hESC-derived hematopoietic cells cocultured with OP9 stromal cells to engraft in both the adult and newborn NOD/SCID mice after intrafemoral and intrahepatic injection illustrated that although OP9 stromal cells augment hESC-derived hematopoiesis and progenitor output, this optimized environment does not confer or augment repopulating function of specified hematopoietic cells derived from hESCs. OP9 coculture also increases hematopoietic progenitors output from hemogenic precursors overexpressing HOXB4. Our study demonstrates that OP9 cells support both hemogenic precursors and their primitive hematopoietic progeny, thereby providing the first evidence toward understanding the cellular targets and mechanisms underlying the capacity of OP9 stromal cells to support hematopoiesis from ESCs and define the future steps required to achieve the global goal of generating bona fide human hematopoietic stem cells from ESC lines.
File Format	HTM / HTML
ISSN	10665099
Issue Number	10
Volume Number	26
e-ISSN	15494918
Journal	STEM CELLS
Language	English
Publisher	Wiley
Publisher Date	2008-10-01
Publisher Place	United States
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Discipline Cell Biology Discipline Embryology Embryonic Stem Cells Cytology Hematopoiesis Hematopoietic Stem Cells Stromal Cells Animals Animals, Newborn Antigens, Cd34 Metabolism Antigens, Cd45 Apoptosis Cell Line Cell Proliferation Cell Separation Cell Survival Coculture Techniques Homeodomain Proteins Humans Mice Transcription Factors Journal Article
Content Type	Text
Resource Type	Article
Subject	Cell Biology Developmental Biology Medicine Molecular Medicine

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OP9 Stroma Augments Survival of Hematopoietic Precursors and Progenitors During Hematopoietic Differentiation from Human Embryonic Stem Cells

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OP9 Stroma Augments Survival of Hematopoietic Precursors and Progenitors During Hematopoietic Differentiation from Human Embryonic Stem Cells