The inherent differentiation program of short-term hematopoietic repopulating cells changes during human ontogeny

• Verfasst von: Tacke, Marlene [VerfasserIn]
• Verfasst von: Ball, Claudia R. [VerfasserIn]
• Verfasst von: Schmidt, Manfred [VerfasserIn]
• Verfasst von: Klingenberg, Silke [VerfasserIn]
• Verfasst von: Maurer, Birgitta [VerfasserIn]
• Verfasst von: Fessler, Sylvia [VerfasserIn]
• Verfasst von: Eaves, Connie J. [VerfasserIn]
• Verfasst von: Kalle, Christof von [VerfasserIn]
• Verfasst von: Glimm, Hanno [VerfasserIn]
• Titel: The inherent differentiation program of short-term hematopoietic repopulating cells changes during human ontogeny
• Verf.angabe: Marlene Tacke, Claudia R. Ball, Manfred Schmidt, Silke Klingenberg, Birgitta Maurer, Sylvia Fessler, Connie J. Eaves, Christof von Kalle, and Hanno Glimm
• Jahr: 2010
• Umfang: 8 S.
• Fussnoten: Erstmals am 29 Sep 2009 online veröffentlicht ; Gesehen am 14.09.2023
• Titel Quelle: Enthalten in: Stem Cells and Development
• Ort Quelle: Larchmont, NY : Liebert, 2004
• Jahr Quelle: 2010
• Band/Heft Quelle: 19(2010), 5 vom: Mai, Seite 621-628
• ISSN Quelle: 1557-8534
• DOI: doi:10.1089/scd.2009.0202
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1859499589

Abstract

Human umbilical cord blood (CB) could be an attractive source of hematopoietic repopulating cells for clinical stem cell therapy because of its accessibility and low propensity for unwanted immune reaction against the host. However, CB recipients suffer from severely delayed and often chronically deficient platelet recovery of unknown cause. Here we show that human short-term repopulating cells (STRCs), which predominantly carry early hematopoietic reconstitution after transplantation, display an intrinsically fixed differentiation program in vivo that changes during ontogeny. Compared to adult sources of hematopoietic cells, CB myeloid-restricted STRC-M showed a markedly reduced megakaryocytic and erythroid cell output in the quantitative xenotransplantation of human short-term hematopoiesis in NOD/SCID-β2m-/- mice. This output in vivo was not altered by pre-treating CB cells before transplantation with growth factors that effectively stimulate megakaryocytopoiesis in vitro. Moreover, injecting mice with granulocyte colony-stimulating factor did not affect the differentiation of human STRC. These findings demonstrate that the differentiation capacity of human STRCs is developmentally regulated by mechanisms inaccessible to currently available hematopoietic growth factors, and explain why thrombopoiesis is deficient in clinical CB transplantation.