ArticleProceedings of the National Academy of Sciences of the United States of America1998
Reduction in levels of the cyclin-dependent kinase inhibitor p27(kip-1) coupled with transforming growth factor beta neutralization induces cell-cycle entry and increases retroviral transduction of primitive human hematopoietic cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 115 citations in OpenAlex.
- Isolation, Maintenance and Expansion of Adult Hematopoietic Stem/Progenitor Cells and Leukemic Stem Cells.Cancers · 2022Review
- Deconstructing the Complexity of TGFβ Signaling in Hematopoietic Stem Cells: Quiescence and Beyond.Current stem cell reports · 2016Article
- Label-retaining, quiescent globose basal cells are found in the olfactory epithelium.The Journal of comparative neurology · 2014Article
- Mesenchymal stem cells for trinucleotide repeat disorders.Methods in molecular biology (Clifton, N.J.) · 2013Article
- Directing mesenchymal stem cells to bone to augment bone formation and increase bone mass.Nature medicine · 2012Article
- Transient silencing of PTEN in human CD34(+) cells enhances their proliferative potential and ability to engraft immunodeficient mice.Experimental hematology · 2012Article
- Hematopoietic stem cells: transcriptional regulation, ex vivo expansion and clinical application.Current molecular medicine · 2012Review
- Review
- Transient inhibition of transforming growth factor-beta1 in human diabetic CD34+ cells enhances vascular reparative functions.Diabetes · 2010Article
- Contribution of human hematopoietic stem cells to liver repair.Seminars in immunopathology · 2009Review
- The TEL-AML1 leukemia fusion gene dysregulates the TGF-beta pathway in early B lineage progenitor cells.The Journal of clinical investigation · 2009Article
- In vivo biosafety model to assess the risk of adverse events from retroviral and lentiviral vectors.Molecular therapy : the journal of the American Society of Gene Therapy · 2008Article
- Fluorophore-conjugated iron oxide nanoparticle labeling and analysis of engrafting human hematopoietic stem cells.Stem cells (Dayton, Ohio) · 2008Article
- Review
- Hematopoiesis and thymic apoptosis are not affected by the loss of Cdk2.Molecular and cellular biology · 2007Article
- Article
- In vivo distribution of human adipose-derived mesenchymal stem cells in novel xenotransplantation models.Stem cells (Dayton, Ohio) · 2007Article
- Azacytidine (Vidaza(R)) in the treatment of myelodysplastic syndromes.Therapeutics and clinical risk management · 2006Article
- Article
- Silencing p21(Waf1/Cip1/Sdi1) expression increases gene transduction efficiency in primitive human hematopoietic cells.Gene therapy · 2005Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
Successful gene therapy depends on stable transduction of hematopoietic stem cells. Target cells must cycle to allow integration of Moloney-based retroviral vectors, yet hematopoietic stem cells are quiescent. Cells can be held in quiescence by intracellular cyclin-dependent kinase inhibitors. The cyclin-dependent kinase inhibitor p15(INK4B) blocks association of cyclin-dependent kinase (CDK)4/cyclin D and p27(kip-1) blocks activity of CDK2/cyclin A and CDK2/cyclin E, complexes that are mandatory for cell-cycle progression. Antibody neutralization of beta transforming growth factor (TGFbeta) in serum-free medium decreased levels of p15(INK4B) and increased colony formation and retroviral-mediated transduction of primary human CD34(+) cells. Although TGFbeta neutralization increased colony formation from more primitive, noncycling hematopoietic progenitors, no increase in M-phase-dependent, retroviral-mediated transduction was observed. Transduction of the primitive cells was augmented by culture in the presence of antisense oligonucleotides to p27(kip-1) coupled with TGFbeta-neutralizing antibodies. The transduced cells engrafted immune-deficient mice with no alteration in human hematopoietic lineage development. We conclude that neutralization of TGFbeta, plus reduction in levels of the cyclin-dependent kinase inhibitor p27, allows transduction of primitive and quiescent hematopoietic progenitor populations.
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