| Selectively increased growth of fetal hemoglobin-expressing adult erythroid progenitors after brief treatment of early progenitors with transforming growth factor beta. | |
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MedLine Citation:
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PMID: 10779447 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We have studied the effect of transforming growth factor beta (TGFbeta) on erythropoiesis in cultures from adult peripheral blood, using flow cytometric enumeration of fetal hemoglobin (HbF)-containing cells. TGFbeta caused a dramatic increase in the proportions of cells that accumulated HbF together with adult hemoglobin (HbA) (F+A+ cells). This highly significant (P <.0001) increase in F+ cell proportion was achieved by TGFbeta treatment during the first 4 days of culture and was sustained during further culture expansion in the absence of TGFbeta. The increase in F+ cell proportions did not depend on the cytokine combination (EPO+SCF+IL3, EPO+SCF, EPO+IL3, SCF+IL3) used during the phase of TGFbeta treatment. Increased F+ cell proportions were paralleled by an increased molecular ratio of HbF/ HbF+ HbA, measured by cation exchange high-performance liquid chromatography (HPLC). In addition to the effect on F+ cell proportions, TGFbeta caused a dramatic increase in overall cell division potential. By the time cultures reached terminal growth arrest (12-14 days in controls and 18-26 days after TGFbeta), the overall numbers of F+ cells produced per initially seeded clonogenic cell was approximately 10 times higher in the TGFbeta-treated cultures than in the controls. We propose to investigate whether the TGFbeta-induced increase in relative and absolute numbers of nucleated F+ cells, as demonstrated in vitro, can be translated into increased F+ erythrocytes in vivo, allowing therapeutic application for some beta-hemoglobinopathies. (Blood. 2000;95:2967-2974) |
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Authors:
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R M Bohmer; T A Campbell; D W Bianchi |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Blood Volume: 95 ISSN: 0006-4971 ISO Abbreviation: Blood Publication Date: 2000 May |
Date Detail:
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Created Date: 2000-05-23 Completed Date: 2000-05-23 Revised Date: 2008-11-21 |
Medline Journal Info:
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Nlm Unique ID: 7603509 Medline TA: Blood Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 2967-74 Citation Subset: AIM; IM |
Affiliation:
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Division of Genetics, Department of Pediatrics, New England Medical Center and Tufts University Medical School, Boston, MA 02111, USA. ralph.bohmer@es.nemc.org |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adult Cell Division / drug effects Cells, Cultured Erythroid Precursor Cells / cytology*, drug effects, metabolism* Fetal Hemoglobin / metabolism* Hemoglobin A / metabolism* Humans Kinetics Time Factors Transforming Growth Factor beta / pharmacology* |
| Chemical | |
Reg. No./Substance:
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0/Transforming Growth Factor beta; 9034-51-9/Hemoglobin A; 9034-63-3/Fetal Hemoglobin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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