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Embryonic Stem Cells/Induced Pluripotent Stem Cells
Inability of Human Induced Pluripotent Stem Cell-Hematopoietic Derivatives to Downregulate MicroRNAs In Vivo Reveals a Block in Xenograft Hematopoietic Regeneration†‡§
Article first published online: 18 JAN 2012
DOI: 10.1002/stem.1684
Copyright © 2011 AlphaMed Press
Additional Information
How to Cite
Risueño, R. M., Sachlos, E., Lee, J.-H., Lee, J. B., Hong, S.-H., Szabo, E. and Bhatia, M. (2012), Inability of Human Induced Pluripotent Stem Cell-Hematopoietic Derivatives to Downregulate MicroRNAs In Vivo Reveals a Block in Xenograft Hematopoietic Regeneration. STEM CELLS, 30: 131–139. doi: 10.1002/stem.1684
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Author contributions: R.M.R.: conception and design, collection and/or assembly of data, data analysis and interpretation, and manuscript writing, E.S.: conception and design, collection and/or assembly of data, data analysis and interpretation, and manuscript writing, J.-H.L., J.B.L., S.-H.H, and E. Szabo: collection and/or assembly of data and data analysis and interpretation; M.B.: conception and design, financial support, data analysis and interpretation, manuscript writing, and final approval of the manuscript. R.M.R. and E.S. contributed equally to this article.
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Disclosure of potential conflicts of interest is found at the end of this article.
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First published online in STEM CELLSEXPRESS November 30, 2011.
Publication History
- Issue published online: 18 JAN 2012
- Article first published online: 18 JAN 2012
- Accepted manuscript online: 30 NOV 2011 01:47PM EST
- Manuscript Accepted: 11 NOV 2011
- Manuscript Received: 11 AUG 2011
Funded by
- Canada Research Chair in human stem cell biology
- TTF fellowship (CCSRI)
- Ministry of Research and Innovation fellowship
Keywords:
- Induced pluripotent stem cells;
- Hemopoietic stem cells;
- Xenogeneic stem cell transplantation;
- MicroRNA;
- Differentiation
Abstract
Hematopoietic stem cells (HSCs) can regenerate the entire hematopoietic system in vivo, providing the most relevant criteria to measure candidate HSCs derived from human embryonic stem cell (hESC) or induced pluripotent stem cell (hiPSC) sources. Here we show that, unlike primitive hematopoietic cells derived from hESCs, phenotypically identical cells derived from hiPSC are more permissive to graft the bone marrow of xenotransplantation recipients. Despite establishment of bone marrow graft, hiPSC-derived cells fail to demonstrate hematopoietic differentiation in vivo. However, once removed from recipient bone marrow, hiPSC-derived grafts were capable of in vitro multilineage hematopoietic differentiation, indicating that xenograft imparts a restriction to in vivo hematopoietic progression. This failure to regenerate multilineage hematopoiesis in vivo was attributed to the inability to downregulate key microRNAs involved in hematopoiesis. Based on these analyses, our study indicates that hiPSCs provide a beneficial source of pluripotent stem cell-derived hematopoietic cells for transplantation compared with hESCs. Since use of the human–mouse xenograft models prevents detection of putative hiPSC-derived HSCs, we suggest that new preclinical models should be explored to fully evaluate cells generated from hiPSC sources. STEM CELLS 2012; 30:131–139.