School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol, United Kingdom.
Blood. 2024 Nov 28;144(22):2283-2294. doi: 10.1182/blood.2024024601.
Platelets play crucial roles in hemostasis, thrombosis, and immunity, but our understanding of their complex biogenesis (thrombopoiesis) is currently incomplete. Deeper insight into the mechanisms of platelet biogenesis inside and outside the body is fundamental for managing hematological disorders and for the development of novel cell-based therapies. In this article, we address the current understanding of in vivo thrombopoiesis, including mechanisms of platelet generation from megakaryocytes (proplatelet formation, cytoplasmic fragmentation, and membrane budding) and their physiological location. Progress has been made in replicating these processes in vitro for potential therapeutic application, notably in platelet transfusion and bioengineering of platelets for novel targeted therapies. The current platelet-generating systems and their limitations, particularly yield, scalability, and functionality, are discussed. Finally, we highlight the current controversies and challenges in the field that need to be addressed to achieve a full understanding of these processes, in vivo and in vitro.
血小板在止血、血栓形成和免疫中起着至关重要的作用,但我们对其复杂的生物发生(即血小板生成)的理解目前还不完全。深入了解体内和体外血小板生物发生的机制对于管理血液疾病和开发新型基于细胞的疗法至关重要。在本文中,我们探讨了目前对体内血小板生成的理解,包括巨核细胞中血小板的生成机制(伸展出的伪足、细胞质分裂和细胞膜出芽)及其生理位置。在体外复制这些过程以进行潜在的治疗应用方面已经取得了进展,特别是在血小板输注和新型靶向治疗的血小板生物工程方面。讨论了当前的血小板生成系统及其局限性,特别是产量、可扩展性和功能。最后,我们强调了该领域目前存在的争议和挑战,需要解决这些问题才能全面了解这些体内和体外的过程。