Thrombopoietin expands hematopoietic stem cells after transplantation

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Thrombopoietin expands hematopoietic stem cells after transplantation

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dc.contributor.author Fox, Norma en_US
dc.contributor.author Priestley, Greg en_US
dc.contributor.author Papayannopoulou, Thalia en_US
dc.contributor.author Kaushansky, Kenneth en_US
dc.date.accessioned 2009-12-15T21:10:28Z
dc.date.available 2009-12-15T21:10:28Z
dc.date.issued 2002 en_US
dc.identifier.citation Fox N, Priestley G, Papayannopoulou T, Kaushansky K. Thrombopoietin expands hematopoietic stem cells after transplantation. J Clin Invest. 2002;110(3):389-394. en_US
dc.identifier.other 10.1172/JCI15430 en_US
dc.identifier.uri http://www.jci.org/articles/view/15430 en_US
dc.identifier.uri http://hdl.handle.net/1773/15539
dc.description.abstract Multiple lines of evidence indicate that thrombopoietin (TPO) contributes to the development of hematopoietic stem cells (HSC), supporting their survival and proliferation in vitro. To determine whether TPO supports the impressive expansion of HSC observed following transplantation, we transplanted normal marrow cells into lethally irradiated Tpo–/– and Tpo+/+ mice and quantified HSC self-renewal and expansion and hematopoietic progenitor cell homing. Although essentially identical numbers of marrow-associated colony forming unit–culture (a surrogate measure of stem cell homing) were observed in each type of recipient 24 hours following transplantation, we found that a minimum of fourfold greater numbers of marrow cells were required to radioprotect Tpo-null mice than to radioprotect controls. To assess whether long-term repopulating (LTR) HSCs self-renew and expand in Tpo–/– recipients or controls, we performed limiting-dilution secondary transplants using donor cells from the Tpo–/– or Tpo+/+ recipients 5–7.5 weeks following primary transplantation. We found that LTR HSCs expand to levels 10–20 times greater within this time period in normal recipients than in Tpo-null mice and that physiologically relevant amounts of TPO administered to the Tpo–/– recipients could substantially correct this defect. Our results establish that TPO greatly promotes the self-renewal and expansion of HSCs in vivo following marrow transplantation. en_US
dc.description.sponsorship NIH grants R01 CA31615, R01 DK44855, and R01 HL58734 en_US
dc.language.iso en_US en_US
dc.title Thrombopoietin expands hematopoietic stem cells after transplantation en_US
dc.type Article en_US


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