On the Quest for In Vitro Platelet Production by Re-Tailoring the Concepts of Megakaryocyte Differentiation

Abstract

The demand of platelet transfusions is steadily growing worldwide, inter-donor variation, donor dependency, or storability/viability being the main contributing factors to the current global, donor-dependent platelet concentrate shortage concern. In vitro platelet production has been proposed as a plausible alternative to cover, at least partially, the increasing demand. However, in practice, such a logical production strategy does not lack complexity, and hence, efforts are focused internationally on developing large scale industrial methods and technologies to provide efficient, viable, and functional platelet production. This would allow obtaining not only sufficient numbers of platelets but also functional ones fit for all clinical purposes and civil scenarios. In this review, we cover the evolution around the in vitro culture and differentiation of megakaryocytes into platelets, the progress made thus far to bring the culture concept from basic research towards good manufacturing practices certified production, and subsequent clinical trial studies. However, little is known about how these in vitro products should be stored or whether any safety measure should be implemented (e.g., pathogen reduction technology), as well as their quality assessment (how to isolate platelets from the rest of the culture cells, debris, microvesicles, or what their molecular and functional profile is). Importantly, we highlight how the scientific community has overcome the old dogmas and how the new perspectives influence the future of platelet-based therapy for transfusion purposes.

PAR4-Mediated PI3K/Akt and RhoA/ROCK Signaling Pathways Are Essential for Thrombin-Induced Morphological Changes in MEG-01 Cells

“…Moreover, since abnormal morphological changes in platelets are associated with pathophysiological conditions, the regulation of platelet cytoskeletal dynamics must be explored in the process of drug discovery for novel PAR4 antagonists [ 47 ]. However, platelets used for research purposes are currently donor-derived, which is associated with some important limitations in terms of short shelf life, donor dependency, and donor variability [ 24 , 48 ]. Here, we showed that MEG-01 cells functionally express PAR1 and PAR4, and that thrombin induce morphological changes in MEG-01 cells through PAR1 and PAR4 activation, such as that observed in human platelets.…”

The Application of Ethnomedicine in Modulating Megakaryocyte Differentiation and Platelet Counts

“…In recent years, ideas of platelet generation in vitro have been proposed, and many laboratories have successfully differentiated megakaryocytes into platelets in vitro. However, the large-scale production of platelets is still a challenging task in vitro [ 17 ].…”