Megakaryopoiesis and ex vivo differentiation of stem cells into megakaryocytes and platelets

Abstract

Blood agencies worldwide face the same recurring problem of enrolling healthy donors to produce platelet concentrates (PC) to meet the fluctuating demand. Research in stem cell biology has now made possible the production of culture‐derived platelets (CDP) raising the possibility of producing donor‐independent platelets. The aim of this paper was to first review known key concepts about megakaryopoiesis and second to describe efforts done in our laboratory and that of others for the establishment of culture processes for the production of megakaryocytes and platelets from cord blood haematopoietic stem and progenitor cells (HSPC). Recent progresses made with induced pluripotent stem cells (iPSCs) are also presented. Expansion of HSPCs and megakaryocytes can be accomplished by combining thrombopoietin (TPO) and a wide array of other cytokines. However, expansion of HSPCs ex vivo is associated with a rapid loss of megakaryocyte differentiation potential. Optimization of cytokine combinations and concentrations can improve yields and reduce consumption of growth factors. Moreover, the development of inducible megakaryocytic cell lines that can be triggered to undergo terminal megakaryocytic differentiation offers an independent solution to some of the problems associated with megakaryocyte production ex vivo. Functional characterization of platelets produced ex vivo has so far revealed that they form a heterogeneous population with some culture‐derived platelets (CDP) showing normal platelet properties and functions. In summary, functional CDPs can be produced in HSPC‐ and iPSC‐based cultures. Remaining challenges that need to be addressed before culture‐derived PCs can be used to complement blood‐derived PCs are also discussed.