Advances and Challenges in the Ex Vivo Production of Megakaryocytes and Platelets
摘要
The production of platelets ex vivo represents a promising solution to address the growing challenges in platelet transfusion therapies, including limited donor availability, short shelf life, and alloimmunization risks. This chapter reviews the current state and recent advances in generating platelets from various cell sources, with particular emphasis on induced pluripotent stem cells (iPSCs). The key developments in three critical areas will be discussed: cellular sources and their optimization, bioengineering approaches for scaled production, and strategies for generating human leukocyte antigen (HLA)-universal platelets. Recent breakthroughs include the development of turbulence-based bioreactors enabling clinical-scale production and the successful completion of the first in-human trial using iPSC-derived platelets. Emerging understanding of megakaryocyte heterogeneity and its implications for platelet production is also examined. While significant progress has been made, challenges remain in achieving cost-effective, large-scale manufacturing of functional platelets. This chapter also provides insights into current limitations and future directions for advancing this field toward widespread clinical application.