Bone morphogenetic protein 4 contributes to the maintenance of primitive cord blood hematopoietic progenitors in an ex vivo stroma-noncontact co-culture system

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dc.contributor.authorHutton, J.
dc.contributor.authorRozenkov, V.
dc.contributor.authorKhor, F.
dc.contributor.authorD'Andrea, R.
dc.contributor.authorLewis, I.
dc.date.issued2006
dc.description.abstractEstablishment of conditions supporting hematopoietic stem cell (HSC) maintenance and expansion ex vivo is critical for wider clinical application of cord blood (CB) transplantation. AFT024 is a murine fetal liver cell line that expands primitive hematopoietic cells via a process that is not understood. Here we show that bone morphogenic protein 4 (BMP4) is produced by AFT024 and contributes significantly to the maintenance of co-cultured CB-derived primitive cells. Significant amounts of BMP4 mRNA are produced by the supportive AFT024 stromal cell line, and secreted BMP4 protein accumulates in AFT024 conditioned medium. Blockade of BMP4 activity in this coculture model using neutralizing BMP4 monoclonal antibody reduced expansion of primitive CB cells on the basis of phenotypic (CD34(+)CD38(-)) and functional criteria [long-term culture initiating cells (LTC-IC)] and significantly reduced the capacity of the cultured CB stem cells to support repopulation in the nonobese diabetic-severe combined immunodeficiency (NOD-SCID) xenograft model. Therefore, BMP4 is a key growth factor for maintenance of HSC and contributes to the unique properties of the AFT024 stromal noncontact culture.
dc.identifier.citationStem Cells and Development, 2006; 15(6):805-813
dc.identifier.doi10.1089/scd.2006.15.805
dc.identifier.issn1547-3287
dc.identifier.issn1557-8534
dc.identifier.urihttp://hdl.handle.net/2440/35771
dc.language.isoen
dc.publisherMary Ann Liebert Inc Publ
dc.source.urihttps://doi.org/10.1089/scd.2006.15.805
dc.subjectHematopoietic Stem Cells
dc.subjectFetal Blood
dc.subjectAnimals
dc.subjectMice, Inbred NOD
dc.subjectHumans
dc.subjectMice
dc.subjectMice, SCID
dc.subjectBone Morphogenetic Proteins
dc.subjectRNA, Messenger
dc.subjectHematopoietic Stem Cell Transplantation
dc.subjectTransplantation, Heterologous
dc.subjectCoculture Techniques
dc.subjectPolymerase Chain Reaction
dc.subjectBone Morphogenetic Protein 4
dc.titleBone morphogenetic protein 4 contributes to the maintenance of primitive cord blood hematopoietic progenitors in an ex vivo stroma-noncontact co-culture system
dc.typeJournal article
pubs.publication-statusPublished

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