Experimental hematology · 2007
Sites and kinetics of donor thrombopoiesis following transplantation of whole bone marrow and progenitor subsets.
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Li Xiao-Miao, Hu Zhongbo, Sola-Visner Martha, Hensel Stacey, Garner Rachel, Zafar Abu-Bakr, Wingard John R, Jorgensen Marda L, Fisher Robert C, Scott Edward W, Slayton William B
Аннотация
INTRODUCTION: 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.
CONCLUSION: 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.
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.
CONCLUSION: 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.