Current status of blood ‘pharming’: megakaryoctye transfusions as a source of platelets

Abstract

Purpose of review Donor-derived platelets have proven to be of hemostatic value in many clinical settings. There is a fear that the need for platelets may outgrow the donor pool in first-world countries. Moreover, there are other challenges with donor platelets that add to the impetus to find an alternative platelet source, especially after the megakaryocyte cytokine thrombopoietin was identified. Megakaryocytes have since been differentiated from numerous cell sources and the observed released platelet-like particles (PLPs) have led to calls to develop such products for clinical use. The development of megakaryocytes from embryonic stem cell also supported the concept of developing non-donor-based platelets. Recent findings Several groups have claimed that non-donor-based platelets derived from in vitro-grown megakaryocytes may soon become available to supplement or replace donor-derived products, but their number and quality has been wanting. A possible alternative of directly infusing megakaryocytes that release platelets in the lungs – similar to that recently shown for endogenous megakaryocytes – has been proposed. Summary This review will describe the present state-of-the-art in generating and delivering non-donor-derived platelets. Progress has been slow, but advances in our ability to generate human megakaryocytes in culture, generate PLPs from these cells, and test the functionality of the resultant platelets in vitro and in vivo have identified important remaining challenges and raised alternative potential solutions.

Megakaryocyte ontogeny: Clinical and molecular significance

“…The fourth problem relates to recent initiatives to develop donor-independent sources of platelets to treat patients with thrombocytopenia. The need for such sources is emerging in developed countries due to steadily rising platelet demands coupled with restricted donor supplies [25]. Recent refinements in ex vivo culture of Mk derived from a variety of sources have enhanced feasibility of producing bioactive platelets or Mk for transfusion [25, 26].…”

“…The need for such sources is emerging in developed countries due to steadily rising platelet demands coupled with restricted donor supplies [25]. Recent refinements in ex vivo culture of Mk derived from a variety of sources have enhanced feasibility of producing bioactive platelets or Mk for transfusion [25, 26]. A major limiting factor in this process is the poor proliferative capacity of adult type Mk in culture, despite efficient platelet biogenesis.…”

Reprogramming Megakaryocytes for Controlled Release of Platelet-like Particles Carrying a Single-Chain Thromboxane A2 Receptor-G-Protein Complex with Therapeutic Potential

“…The therapeutic impact of PLPs has been well documented; for example, PLPs have shown the ability to improve wound healing [28,29]. Several groups have suggested that non-donor-based platelets derived from in vitro-grown megakaryocytes may serve as supplements to donor-derived platelets [30]. While the therapeutic potentials of nucleus-free PLPs have been previously demonstrated, the majority of the studies are limited to the applications of "mimicking platelet functions.…”

Effects of thrombopoietin pre-treatment on peri-liver transplantation thrombocytopenia in a mouse model of cirrhosis with hypersplenism

“…These findings suggest that, in patients with liver failure, TPO plays a critical role in thrombocytopenia and in the restoration of platelet count after liver transplantation. Gollomp et al [ 6 ] found similar serum TPO levels before and after liver transplantation, as well as significantly lower TPO mRNA expressions in the liver tissues of patients with cirrhosis. Thrombocytopenia in patients with liver failure is challenging.…”