Towards the Manufacture of Megakaryocytes and Platelets for Clinical Application

Abstract

Platelet transfusions are used in standard clinical practice to prevent hemorrhage in patients suffering from thrombocytopenia or platelet dysfunctions. Recently, a constant rise on the demand of platelets for transfusion has been registered. This may be associated with several factors including demographic changes, population aging as well as incidence and prevalence of hematological diseases. In addition, platelet-regenerative properties have been started to be exploited in different areas such as tissue remodeling and anti-cancer therapies. These new applications are also expected to increase the future demand on platelets. Thus, in vitro generated platelets may constitute a highly desirable alternative to meet the rising demand on platelets. Several factors have been considered in the road trip of producing in vitro megakaryocytes and platelets for clinical application. From selection of the cell source, differentiation protocols and culture conditions to the design of optimal bioreactors, several strategies have been proposed to maximize production yields while preserving functionality. This review summarizes new advances in megakaryocyte and platelet differentiation and their production upscaling.

Genomeditierung in der Zell- und Gentherapie

“…Aus Patientenzellen abgeleitete iPS-Zellen erlauben daher nicht nur die Erzeugung personalisierter In-vitro-Krankheitsmodelle, sie ermöglichen auch die patientenspezifische Arzneimitteltestung, die Validierung von Genomeditierstrategien vor (prä-)klinischer Prüfung und letztlich die Herstellung autologer Zelltherapeutika für die regenerative Medizin. Als zelltherapeutisches Fachgebiet ist die Transfusionsmedizin daher prädestiniert, an der klinischen Umsetzung der Genomeditierung und der iPS-Zelltechnologie gestaltend und einflussnehmend mitzuwirken [12][13][14][15].…”

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

“…Non-donor platelets also offer the possibility of generating a more uniform product with known consistent clinical outcomes per transfused unit [4]. Donor-derived platelets units have a marked variability in response to agonists [5] as well as different yields per unit [6] (see Table 1 comparing donor-derived versus in vitro-derived platelets).…”

“…Subsequently several groups have presented data on plastic-based bioreactors [4,38,39] (Figure 2). While acknowledging the potential value of an endothelial lined system for physiologic platelet generation [39], none of the actual systems tested used to generate PLPs were coated with endothelial cells.…”

Previews

“…The platelets (or thrombocytes) present in mammalian blood react to bleeding by initiating blood clotting with the help of various coagulation factors; therefore, patients presenting with defective platelets or low blood platelet counts (thrombocytopenia) are at high risk of spontaneous bleeding or poor responses to surgical procedures. Human volunteer donors currently represent the source of platelets for transfusions, although this approach is limited by various concerns, including the requirement for storage conditions, fluctuating supply, the risk of contamination, and immune‐related concerns . To solve this problem, researchers have sought to isolate and culture CD34‐positive hematopoietic stem/progenitor cells (HSPCs) from various sources to then generate the megakaryocytes that eventually produce proplatelets, the precursors to platelets .…”