Recombinant HoxB4 fusion proteins enhance hematopoietic differentiation of human embryonic stem cells.

Recombinant HoxB4 fusion proteins enhance hematopoietic differentiation of human embryonic stem cells. Research Abstract Details 

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Recombinant HoxB4 fusion proteins enhance hematopoietic differentiation of human embryonic stem cells. Abstract Text:

Shi-Jiang Lu,Qiang Feng,Yordanka Ivanova,Chenmei Luo,Tong Li,Fei Li,George R Honig,Robert Lanza,Shi-Jiang Lu,Qiang Feng,Yordanka Ivanova,Chenmei Luo,Tong Li,Fei Li,George R Honig,Robert Lanza,

Enforced expression of the HoxB4 gene promotes expansion of hematopoietic stem cells (HSCs) and enhances hematopoietic development of both murine and human embryonic stem (ES) cells. HoxB4- expanded HSCs have also been shown to retain their normal potential for differentiation and longterm self-renewal in vivo without the development of leukemia, suggesting that manipulation of HoxB4 expression might represent an effective way to expand functional HSCs for use in transplantation medicine. However, the genetic modification of cells poses clinical concerns, including a potentially increased risk of tumor genicity. Constitutive high-level ectopic viral expression of HoxB4 can also produce perturbations in the lineage differentiation of HSCs, an indication that uncontrolled HoxB4 manipulation may not be a satisfactory therapeutic strategy. Here we demonstrate that recombinant HoxB4 protein fused with a triple protein transduction domain (tPTD) promotes hematopoietic development of hES cells. The tPTD-HoxB4 protein enhanced the development of erythroid, myeloid, and multipotential progenitors in both early- and late-stage embryoid bodies (EBs). This effect varied considerably between different hES cell lines. Addition of the tPTD-HoxB4 protein did not alter the globin gene expression pattern; progeny derived from hES cells expressed high levels of embryonic (epsilon) and fetal (gamma) globin genes with or without tPTD-HoxB4 treatment. CD34+ cells derived from hES cells engrafted in bone marrow when transplanted into fetal CD1 mice, although supplementation of the differentiation medium with tPTD-HoxB4 protein did not result in increased repopulating capacity. This suggests that other gene(s), together with HoxB4, are required for generating more competitive HSCs. In summary, our study demonstrates that the tPTD-HoxB4 protein can be used with other recombinant proteins to efficiently generate transplantable HSCs from human ES cells.

Recombinant HoxB4 fusion proteins enhance hematopoietic differentiation of human embryonic stem cells. Publishing Authors By Initials

SJ Lu,Q Feng,Y Ivanova,C Luo,T Li,F Li,GR Honig,R Lanza,SJ Lu,Q Feng,Y Ivanova,C Luo,T Li,F Li,GR Honig,R Lanza,

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Recombinant HoxB4 fusion proteins enhance hematopoietic differentiation of human embryonic stem cells. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Stem cells and development

VOLUME: 16

Page Numbers: 547-59

Journal Abbreviation: Stem Cells Dev.

ISSN: 1547-3287

DAY: 5

MONTH: Aug

YEAR: 2007

Recombinant HoxB4 fusion proteins enhance hematopoietic differentiation of human embryonic stem cells. Information

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LANGUAGE: eng

NlmUniqueID: 101197107

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AFFILIATION: Advanced Cell Technology, Worcester, MA 01605, USA.

Country: United States

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MEDLINETA: Stem Cells Dev

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