CXCR4 induction in hematopoietic progenitor cells from Fanca(-/-), -c(-/-), and -d2(-/-) mice.

CXCR4 induction in hematopoietic progenitor cells from Fanca(-/-), -c(-/-), and -d2(-/-) mice. Research Abstract Details 

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CXCR4 induction in hematopoietic progenitor cells from Fanca(-/-), -c(-/-), and -d2(-/-) mice. Abstract Text:

Amy M Skinner,S Lee O'Neill,Markus Grompe,Peter Kurre,

OBJECTIVE: Bone marrow failure is a near-universal occurrence in patients with Fanconi anemia (FA) and is thought to result from exhaustion of the hematopoietic stem cell (HSC) pool. Retrovirus-mediated expression of the deficient protein corrects this phenotype and makes FA a candidate disease for HSC-directed gene therapy. However, inherent repopulation deficits and stem cell attrition during conventional transduction culture prevent therapeutic chimerism. MATERIALS AND METHODS: We previously reported rapid transduction protocols to limit stem cell losses after ex vivo culture. Here we describe a complementary strategy intended to improve repopulation through upregulation of chemokine receptor (CXCR) 4, a principal factor in hematopoietic homing. RESULTS: Using murine models with transgenic disruption of Fanca, -c, and -d2, we found that c-kit(+) and sca-1(+) progenitor cells express levels of CXCR4 comparable with those of wild-type littermates. Lineage-depleted progenitor populations rapidly upregulated CXCR4 transcript and protein in response to cytokine stimulation or hypoxia, regardless of genotype. Hypoxia conditioning of lineage-depleted Fancc(-/-) progenitors also reduced oxidative stress, improved in vitro migration and led to improved chimerism in myeloablated recipients after transplantation. CONCLUSION: These studies provide evidence that CXCR4 regulation in progenitor cells from transgenic mice representing multiple FA genotypes is intact and that modulation of homing offers a potential strategy to offset the FA HSC repopulation deficiency.

CXCR4 induction in hematopoietic progenitor cells from Fanca(-/-), -c(-/-), and -d2(-/-) mice. Publishing Authors By Initials

AM Skinner,SL O'Neill,M Grompe,P Kurre,

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CXCR4 induction in hematopoietic progenitor cells from Fanca(-/-), -c(-/-), and -d2(-/-) mice. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Experimental hematology

VOLUME: 36

Page Numbers: 273-82

Journal Abbreviation: Exp. Hematol.

ISSN: 0301-472X

DAY: 18

MONTH: Mar

YEAR: 2008

CXCR4 induction in hematopoietic progenitor cells from Fanca(-/-), -c(-/-), and -d2(-/-) mice. Information

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LANGUAGE: eng

NlmUniqueID: 402313

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Grant and Affiliation Information for CXCR4 induction in hematopoietic progenitor cells from Fanca(-/-), -c(-/-), and -d2(-/-) mice.

AFFILIATION: Department of Pediatrics, Oregon Health and Science University, Portland, Ore., USA.

Country: Netherlands

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MEDLINETA: Exp Hematol

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