Sites and kinetics of donor thrombopoiesis following transplantation of whole bone marrow and progenitor subsets

• Published in: Experimental hematology 2007-10, Vol.35 (10), p.1567-1579
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: Advanced Basic Science; Animals; Antigens, Ly - biosynthesis; Antigens, Ly - immunology; Bone Marrow Transplantation; Graft Survival - immunology; Graft Survival - radiation effects; Hematology, Oncology and Palliative Medicine; Hematopoiesis, Extramedullary - immunology; Hematopoiesis, Extramedullary - radiation effects; Hypersplenism - immunology; Hypersplenism - metabolism; Hypersplenism - pathology; Kinetics; Male; Megakaryocytes - immunology; Megakaryocytes - metabolism; Megakaryocytes - pathology; Membrane Proteins - biosynthesis; Membrane Proteins - immunology; Mice; Mice, Transgenic; Proto-Oncogene Proteins c-kit - biosynthesis; Proto-Oncogene Proteins c-kit - immunology; Spleen - immunology; Spleen - metabolism; Spleen - pathology; Thrombopoiesis - immunology; Thrombopoiesis - radiation effects; Time Factors; Whole-Body Irradiation
• ISSN: 0301-472X; 1873-2399
• DOI: 10.1016/j.exphem.2007.06.011

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.