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

MH Ledran; A Krassowska; L Armstrong; I Dimmick; J Renstrom; R Lang; S Yung; M Santibanez-Coref; Elaine Dzierzak; M Stojkovic; RAJ (Robert) Oostendorp; L Forrester; M Lako

doi:10.1016/j.stem.2008.06.001

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

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

Cell biology

Research output: Contribution to journal › Article › Academic

264 Citations (Scopus)

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.

Original language	Undefined/Unknown
Pages (from-to)	85-98
Number of pages	14
Journal	Cell Stem Cell
Volume	3
Issue number	1
DOIs	https://doi.org/10.1016/j.stem.2008.06.001
Publication status	Published - 2008

Research programs

EMC MGC-02-13-03

Access to Document

10.1016/j.stem.2008.06.001

http://hdl.handle.net/1765/33121

Cite this

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. (2008). Efficient hematopoietic differentiation of human embryonic stem cells on stromal cells derived from hematopoietic niches. Cell Stem Cell, 3(1), 85-98. https://doi.org/10.1016/j.stem.2008.06.001

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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.",

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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 2008, 'Efficient hematopoietic differentiation of human embryonic stem cells on stromal cells derived from hematopoietic niches', Cell Stem Cell, vol. 3, no. 1, pp. 85-98. https://doi.org/10.1016/j.stem.2008.06.001

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T1 - Efficient hematopoietic differentiation of human embryonic stem cells on stromal cells derived from hematopoietic niches

AU - Ledran, MH

AU - Krassowska, A

AU - Armstrong, L

AU - Dimmick, I

AU - Renstrom, J

AU - Lang, R

AU - Yung, S

AU - Santibanez-Coref, M

AU - Dzierzak, Elaine

AU - Stojkovic, M

AU - Oostendorp, RAJ (Robert)

AU - Forrester, L

AU - Lako, M

PY - 2008

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AB - 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.

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DO - 10.1016/j.stem.2008.06.001

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