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TISSUE-SPECIFIC STEM CELLS

Thrombopoietin Enhances Generation of CD34+ Cells from Human Embryonic Stem Cells

^aMoores UCSD Cancer Center, Department of Medicine, University of California San Diego, San Diego, California, USA;
^bDepartment of Pathology, University of California Los Angeles, Los Angeles, California, USA;
^cDNAmicroarray, Inc., San Diego, California, USA;
^dDivision of Nephrology, Department of Medicine, Case Western Reserve University, Cleveland, Ohio, USA

Key Words. Human embryonic stem cells • CD34+ progenitors • Hematopoietic progenitors • CD31+ progenitors

Correspondence: Ewa Carrier, M.D., Department of Medicine, Pediatrics and UCSD Moores Cancer Center, School of Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA. Telephone: 858-822-6848; Fax: 858-822-6844; e-mail: ecarrier{at}ucsd.edu

Received November 3, 2006; accepted for publication March 8, 2007.
First published online in STEM CELLS EXPRESS   March 22, 2007.



The role of thrombopoietin (TPO) in adult hematopoiesis is well-established. A recent report suggests that TPO and vascular endothelial growth factor (VEGF) play a role in promoting formation of early erythropoietic progenitors in a nonhuman primate embryonic stem cell (ES) model. No such report exists for human ES cells as yet. Because TPO may become an important factor promoting human ES cell-derived hematopoiesis, we sought to investigate whether TPO in combination with VEGF can enhance human ES-derived hematopoiesis in an EB-derived culture system. The emphasis of this work was to demonstrate the molecular mechanisms involved in this process, specifically the role of c-mpl and its ligand TPO. Human ES cells were cultured to the EB state, and EB-derived secondary cultures supporting hematopoietic differentiation were established: condition 1, control (stem cell factor [SCF] and Flt3 ligand [Flt3L]); condition 2, SCF, Flt3L, and TPO; and condition 3, SCF, Flt3L, TPO, and VEGF. Cells were harvested daily, starting at day 2 and continuing until day 8, for reverse transcription-polymerase chain reaction and Western blot. There was no evidence of expression of c-mpl and VEGF receptor on the gene or protein level until day 8, when the formation of well-established hematopoietic colonies began. This correlated with the formation of CD34+/CD31– negative progenitors, mostly found in blast-forming units-erythroid-like colonies. We concluded that TPO and VEGF play an important synergistic role in the formation of early ES-derived hematopoietic progenitors that occurs through the c-mpl and VEGF receptors.

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

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