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Efficient hematopoietic differentiation of human embryonic stem cells on stromal cells derived from hematopoietic niches

Lookup NU author(s): Dr Maria Ledran, Professor Lyle Armstrong, Ian Dimmick, Dr Rebecca Lang, Sun Yung, Dr Mauro Santibanez Koref, Professor Miodrag Stojkovic, Professor Majlinda Lako

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Abstract

Hematopoietic stem cells derived from human embryonic stem cells (hESCs) could provide a therapeutic alternative to bone marrow transplants, but the efficiency of currently available derivation protocols is low. In this study, we investigated whether coculture with monolayers; of cells derived from mouse AGM and fetal liver, or with stromal cell lines derived from these tissues, can enhance hESC hematopoietic differentiation. We found that under such conditions hESC-derived differentiating cells formed early hematopoietic progenitors, with a peak at day 18-21 of differentiation that corresponded to the highest CD34 expression. These hESC-derived hematopoietic cells were capable of primary and secondary hematopoietic engraftment into immunocompromised mice at substantially higher levels than described previously. Transcriptional and functional analysis identified TGF-beta 1 and TGF-beta 3 as positive enhancers of hESC hematopoietic differentiation that can further stimulate this process when added to the culture. Overall, our findings represent significant progress toward the goal of deriving functional hematopoietic stem cells from hESCs.


Publication metadata

Author(s): Ledran MH, Krassowska A, Armstrong L, Dimmick I, Renstrom J, Lang R, Yung S, Santibanez-Coref M, Dzierzak E, Stojkovic M, Oostendorp RAJ, Forrester L, Lako M

Publication type: Article

Publication status: Published

Journal: Cell Stem Cell

Year: 2008

Volume: 3

Issue: 1

Pages: 85-98

ISSN (electronic): 1934-5909

Publisher: Cell Press

URL: http://dx.doi.org/10.1016/j.stem.2008.06.001

DOI: 10.1016/j.stem.2008.06.001


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