血小板生成素
诱导多能干细胞
血小板
离体
再生医学
血小板输注
人类白细胞抗原
免疫学
输血医学
干细胞
生物
医学
体内
抗原
巨核细胞
生物技术
细胞生物学
造血
输血
胚胎干细胞
基因
遗传学
作者
Naoshi Sugimoto,Koji Eto
摘要
Ex vivo production of human platelets has been pursued as an alternative measure to resolve limitations in the supply and safety of current platelet transfusion products. To this end, induced pluripotent stem cells (iPSCs) are considered an ideal global source, as they are not only pluripotent and self-renewing, but are also available from basically any person, have relatively few ethical issues, and are easy to manipulate. From human iPSCs, megakaryocyte (MK) lines with robust proliferation capacity have been established by the introduction of specified sets of genes. These expandable MKs are also cryopreservable and thus would be suitable as master cells for good manufacturing practice (GMP)-grade production of platelets, assuring availability on demand and safety against blood-borne infections. Meanwhile, developments in bioreactors that physically mimic the in vivo environment and discovery of substances that promote thrombopoiesis have yielded competent platelets with improved efficiency. The derivation of platelets from iPSCs could further resolve transfusion-related alloimmune complications through the manufacturing of autologous products and human leukocyte antigen (HLA)-compatible platelets from stocked homologous HLA-type iPSC libraries or by manipulation of HLAs and human platelet antigens (HPAs). Considering these key advances in the field, HLA-deleted platelets could become a universal product that is manufactured at industrial level to safely fulfill almost all demands. In this review, we provide an overview of the ex vivo production of iPSC-derived platelets toward clinical applications, a production that would revolutionize the blood transfusion system and lead the field of iPSC-based regenerative medicine.
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