HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) An erratum has been published All Versions of this Article: 2008-0642v1 26/10/2485    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints/Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Ji, J. Articles by Bhatia, M. Search for Related Content PubMed PubMed Citation Articles by Ji, J. Articles by Bhatia, M.

EMBRYONIC STEM CELLS/INDUCED PLURIPOTENT STEM CELLS

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

^aMcMaster Stem Cell and Cancer Research Institute, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada;
^bUniversitatsklinikum Tubingen, Tubingen, Germany

Key Words. Human embryonic stem cells • Hematopoiesis • OP9 • Stromal cells

Correspondence: Correspondence: Mickie Bhatia, Ph.D., Stem Cell and Cancer Research Institute, Faculty of Health Sciences, McMaster University, 1200 Main Street West, MDCL 5029, Hamilton, Ontario, N6A 5K8, Canada. Telephone: 905-521-2100, ext. 28687; Fax: 905-522-7772; e-mail: mbhatia{at}mcmaster.ca

Received on July 7, 2008; accepted for publication on July 25, 2008.

First published online in STEM CELLS EXPRESS  July 31, 2008.

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.

Disclosure of potential conflicts of interest is found at the end of this article.