Document Detail

Generation of red blood cells from human induced pluripotent stem cells.
MedLine Citation:
PMID:  21434814     Owner:  NLM     Status:  MEDLINE    
Differentiation of human induced pluripotent stem cells (hiPSCs) and embryonic stem cells (hESCs) into the erythroid lineage of cells offers a novel opportunity to study erythroid development, regulation of globin switching, drug testing, and modeling of red blood cell (RBC) diseases in vitro. Here we describe an approach for the efficient generation of RBCs from hiPSC/hESCs using an OP9 coculture system to induce hematopoietic differentiation followed by selective expansion of erythroid cells in serum-free media with erythropoiesis-supporting cytokines. We showed that fibroblast-derived transgenic hiPSCs generated using lentivirus-based vectors and transgene-free hiPSCs generated using episomal vectors can be differentiated into RBCs with an efficiency similar to that of H1 hESCs. Erythroid cultures established with this approach consisted of an essentially pure population of CD235a(+)CD45(-) leukocyte-free RBCs with robust expansion potential and long life span (up to 90 days). Similar to hESCs, hiPSC-derived RBCs expressed predominately fetal γ and embryonic ɛ globins, indicating complete reprogramming of β-globin locus following transition of fibroblasts to the pluripotent state. Although β-globin expression was detected in hiPSC/hESC-derived erythroid cells, its expression was substantially lower than the embryonic and fetal globins. Overall, these results demonstrate the feasibility of large-scale production of erythroid cells from fibroblast-derived hiPSCs, as has been described for hESCs. Since RBCs generated from transgene-free hiPSCs lack genomic integration and background expression of reprogramming genes, they would be a preferable cell source for modeling of diseases and for gene function studies.
Jessica Dias; Marina Gumenyuk; HyunJun Kang; Maxim Vodyanik; Junying Yu; James A Thomson; Igor I Slukvin
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-05-11
Journal Detail:
Title:  Stem cells and development     Volume:  20     ISSN:  1557-8534     ISO Abbreviation:  Stem Cells Dev.     Publication Date:  2011 Sep 
Date Detail:
Created Date:  2011-08-26     Completed Date:  2011-12-14     Revised Date:  2013-06-30    
Medline Journal Info:
Nlm Unique ID:  101197107     Medline TA:  Stem Cells Dev     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1639-47     Citation Subset:  IM    
Department of Pathology and Laboratory Medicine, University of Wisconsin, School of Medicine and Public Health, Madison, Wisconsin 53715, USA.
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MeSH Terms
Antigens, CD / metabolism
Cell Differentiation
Cell Line
Cell Proliferation
Cell Shape
Coculture Techniques
Embryonic Stem Cells / physiology
Erythrocytes / cytology*,  metabolism
Erythroid Cells / metabolism
Flow Cytometry
Hemoglobins / metabolism
Induced Pluripotent Stem Cells / metabolism,  physiology*
Grant Support
P01 GM081629/GM/NIGMS NIH HHS; P01 GM081629/GM/NIGMS NIH HHS; P01 GM081629-030003/GM/NIGMS NIH HHS; P51 RR000167/RR/NCRR NIH HHS; P51 RR000167/RR/NCRR NIH HHS; P51 RR000167-47A16583/RR/NCRR NIH HHS; R01 HL081962/HL/NHLBI NIH HHS; R01 HL081962-04/HL/NHLBI NIH HHS; R01 HL081962-05/HL/NHLBI NIH HHS
Reg. No./Substance:
0/Antigens, CD; 0/Hemoglobins

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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