Cell-derived microparticles (MPs) are vesicles budding from cellular plasma membrane under stress or activation, range from 0.1 to 1 micron in size. MPs are found to be important in cell-cell communication through transferring cargos such as RNAs, proteins, and lipids from parent cells to target cells. We focus on megakaryocytic MPs (MkMPs) derived from human hematopoietic stem and progenitor cells (HSPCs), which is the most abundant MPs in circulating blood. We have previously shown that MkMPs target HSPCs to program them into generating megakaryocytes (Mks) leading to platelet generation without addition of thrombopoietin. The recognition is specific for HSPCs and the outcomes specific for Mk and platelet generation. We have also shown that uptake of MkMPs by HSPCs is though both some endocytic process had membrane fusion. In this presentation, we carried out studies to enhance our understanding of the process of target recognition and specificity with the ultimate goal of using MkMPs for cell therapy and cargo-delivery applications.  Using various inhibitors, we will present data which show that macropinocytosis and lipid rafts play an important role in the uptake of MkMPs by HSPCs. We will also describe that MkMPs target and enter HSPCs in the uropod part of HSPCs, and how we identified the specific surface antigens, mostly on HSPCs, that are responsible of mediating the recognition and uptake process of MkMPs. We will demonstrate the major difference between MkMPs and human platelet-derived MPs (PMPs), specifically on the interaction with HSPCs. Instead of being uptake by HSPCs, PMPs were only binding to HSPCs. To explain this observation, we carried out studies to show that the activation process of human platelets during PMPs generation is largely responsive for the observed differences. In order to pursue therapeutic applications of MkMPs, we will present data our from early studies involving transfusion of MkMPs in a murine model with and without induced thrombocytopenia.

Megakaryocytic microparticles for cell-therapy applications<i>: In vitro</i> & <i>in vivo</i> studies

253rd National Meeting (2017)

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Megakaryocytic microparticles for cell-therapy applications: In vitro & in vivo studies