Comparative analysis of human ex vivo-generated platelets vs. megakaryocyte-generated platelets in mice: A cautionary tale.

Publication Type:

Journal Article

Source:

Blood, Volume 125, Issue 23, p.3627-36 (2015)

Keywords:

Cell Processing Core Facility

Abstract:

Thrombopoiesis is the process by which megakaryocytes release platelets that circulate as uniform small, disc-shaped anucleate cytoplasmic fragments with critical roles in hemostasis and related biologies. The exact mechanism of thrombopoiesis and the maturation pathways of platelets released into the circulation remain incompletely understood. We have shown that ex vivo-generated murine megakaryocytes infused into mice release platelets within the pulmonary vasculature. Here we now show that infused human megakaryocytes also release platelets within the lungs of recipient mice. In addition, we observed a population of platelet-like particles (PLP) in the infusate, which include platelets released during ex vivo growth conditions. By comparing these two platelet populations to human donor platelets, we found marked differences: Platelets derived from infused megakaryocytes closely resembled infused donor platelets in morphology, size and function. On the other hand, the PLP was a mixture of non-platelet cellular fragments, and non-uniform sized, pre-activated platelets lacking surface CD42b that were rapidly cleared by macrophages. These data raise a cautionary note for the clinical use of human platelets released under standard, ex-vivo conditions. In contrast, human platelets released by intrapulmonary entrapped megakaryocytes appear more physiologic in nature and near comparable to donor platelets for clinical application.