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Towards sustained human platelet production for therapeutic use

© Annals of Blood. All rights reserved. Ann Blood 2020 | http://dx.doi.org/10.21037/aob-20-82 Platelet concentrates are transfused for life-saving prophylactic or therapeutic purposes. These include treatment for those thrombocytopenic patients with acute or chronic blood loss, or those undergoing hematopoietic stem cell (HSC) or organ transplantation (1). In 2017, European blood banks issued over 2.9 million platelet concentrates, of which just over 2.28 million were transfused into 317,898 recipients (2). More recent estimates [although these figures are affected by and evolving during the current 2020 SARSCoV2 pandemic (3)] indicate that over 2 million platelet concentrates (around 7,000 per day) are administered per annum to patients in the USA alone (4,5). Although guidelines have been developed for platelet transfusions (1,5,6), and revised recently in the light of a potential scarcity of platelets during the SARS-CoV2 pandemic (3), controversies still exist as to best practice. In less challenging times, one such controversy relates to defining or developing the best platelet product for transfusion. While such platelets are generally sourced from healthy blood donors by apheresis or after isolation and pooling from whole blood (1), they possess a short shelflife (5–7 days at room temperature), have restrictive storage conditions, rely on donor availability, are susceptible to pathogen contamination, and can lead to allo-immunisation to HLA Class I antigens (1,3,5). The prospect that platelet donations may not meet future demands has spurred on research to generate platelets from alternative sources. These include the production of megakaryocytes and platelets from a variety of stem and progenitor cells ex vivo and the development of technologies to manufacture artificial platelets (7-9). Needless to say, platelets once generated ex vivo from stem and progenitor cells would undoubtedly face similar, or possibly even further, limitations related to shelf-life and storage conditions as those sourced directly from donors. However, advantages cited include a lack of reliance on immediate blood donor availability, reduction in the potential risk of pathogen (e.g., viral or variant Creutzfeldt-Jakob disease) transmission, and the potential to reduce their immunogenicity through, for example, genetic modification of the originating stem and progenitor cells (7,8). A number of stem cell studies have concentrated on the use of ES (embryonic stem) or iPS (induced pluripotent stem) cells or immortalised cell lines with megakaryocytic potential for sustained platelet production, incorporating such techniques as forward programing to enhance megakaryocyte and platelet production (7,8). Safety concerns include the propensity for tumor formation through cross-contamination of the platelet products by the originating lines (7,8). An alternative approach is to manufacture and amplify megakaryocytes and their precursors ex vivo after sourcing hematopoietic stem and progenitor cells (HSPCs) from healthy human donors prior to infusion into patients, with platelet production then proceeding in vivo. Indeed, modelling studies in murine or non-human primate models indicate that megakaryocytes Editorial Commentary