title: Sites and kinetics of donor thrombopoiesis following transplantation of whole bone marrow and progenitor subsets.
abstract: BACKGROUND
  Little is known about the sites and kinetics of thrombopoiesis following bone marrow transplant. The spleen is a site of hematopoiesis in a healthy mouse, and hematopoietic activity increases in response to stress. We hypothesized that the spleen is a major site of early post-transplant thrombopoiesis.
  
  
  METHODS
  We transplanted whole bone marrow (WBM) or lineage depleted progenitor subsets fractionated based on expression of c-kit and Sca-1 from transgenic mice expressing green fluorescent protein into lethally irradiated C57BL/6 recipients. We also transplanted whole bone marrow cells into healthy and splenectomized mice. Post-transplant megakaryopoiesis was assessed by measuring circulating platelet number, percent donor-derived platelets, bone marrow cellularity, splenic weight, megakaryocyte size, and megakaryocyte concentration from hour 3 to day 28 post transplant.
  
  
  RESULTS
  Following transplant, circulating donor-derived platelets were derived only from c-kit expressing subsets. Donor-derived platelets first appeared on post-transplant day five. Splenectomy reduced the number of these earliest circulating platelets. Splenic megakaryopoiesis increased dramatically from day 7-14 post-transplant. However, splenectomy accelerated platelet engraftment during this time frame.
  
  
  CONCLUSIONS
  Overall, these results demonstrate that the first platelets are produced by c-kit expressing megakaryocyte progenitors in the bone marrow and spleen. After post-transplant day 5, the net effect of the spleen on thrombopoiesis is to slow engraftment due to immune effects or hypersplenism.
authors: Department of Pediatrics, University of Florida, Gainesville, USA.
authors: Xiao-Miao
authors: XM
authors: Li
authors: Zhongbo
authors: Z
authors: Hu
authors: Martha
authors: M
authors: Sola-Visner
authors: Stacey
authors: S
authors: Hensel
authors: Rachel
authors: R
authors: Garner
authors: Abu-Bakr
authors: AB
authors: Zafar
authors: John R
authors: JR
authors: Wingard
authors: Marda L
authors: ML
authors: Jorgensen
authors: Robert C
authors: RC
authors: Fisher
authors: Edward W
authors: EW
authors: Scott
authors: William B
authors: WB
authors: Slayton
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000096:biosynthesis / Q000276:immunology; D016026:Bone Marrow Transplantation; D006085:Graft Survival / Q000276:immunology / Q000528:radiation effects; D006411:Hematopoiesis, Extramedullary / Q000276:immunology / Q000528:radiation effects; D006971:Hypersplenism / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007700:Kinetics; D008297:Male; D008533:Megakaryocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008565:Membrane Proteins / Q000096:biosynthesis / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis / Q000276:immunology; D013154:Spleen / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D034061:Thrombopoiesis / Q000276:immunology / Q000528:radiation effects; D013997:Time Factors; D014916:Whole-Body Irradiation
chemical_list: D000950:Antigens, Ly; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D019009:Proto-Oncogene Proteins c-kit