In vitro-derived platelets: the challenges we will have to face to assess quality and safety
In vitro-derived platelets: the challenges we will have to face to assess quality and safety
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DOI：
10.1080/09537104.2020.1769051
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发表时间：
2020-06-04
期刊：
影响因子：
3.3
通讯作者：
Ghevaert, C. J.
中科院分区：
文献类型：
--
作者：
Mookerjee, S.;Foster, H. R.;Ghevaert, C. J.
血小板输注是给那些由于大出血（创伤或手术后）或由于化疗、恶性细胞浸润、纤维化或遗传性疾病导致骨髓血小板生成受损而导致血小板计数低（血小板减少症）的住院患者。我们目前完全依赖献血者作为输血医学中血小板的来源。然而，由于人口老龄化、医疗程序的进步和越来越积极的癌症治疗，对血小板的需求继续上升，而献血者的供应继续保持不变。近年来，几个研究小组在体外生成用于人输血的血小板方面取得了重大进展。最近的成功包括产生成熟的人巨核细胞以及开发用于从这些巨核细胞提取血小板的生物反应器的结果。体外制造的血小板可以解决来自献血者的血小板固有的几个问题-根据需求更灵活地扩大/缩小规模的能力，因此不太稳定的供应线，降低暴露于感染因子的风险，最后是工程干细胞以降低免疫原性的可能性。在这里，我们定义了质量控制工具，并提出了在体外血小板生成领域实施的措施，以帮助实验室之间的合作，并帮助监管机构最终要求的有效性和生物安全性的证明责任。首先，我们将通过解决用于制造血小板的有核细胞的质量控制，特别强调安全性问题，其次，我们将研究如何解决血小板功能测量，特别是在体外衍生血小板的背景下。
Platelet transfusions are given to patients in hospital who have a low blood platelet count (thrombocytopenia) either because of major bleeding (following trauma or surgery) or because the bone marrow production of platelets is impaired often due to chemotherapy, infiltration with malignant cells, fibrosis or genetic disorders. We are currently entirely reliant on blood donors as a source of platelets in transfusion medicine. However, the demand for platelets continues to rise, driven by an aging population, advances in medical procedures and ever more aggressive cancer therapies, while the supply of blood donors continues to remain static. In recent years, several groups have made major advances toward the generation of platelets in vitro for human transfusion. Recent successes include results in both generating mature human megakaryocytes as well as in developing bioreactors for extracting platelets from these megakaryocytes. Platelets made in vitro could address several issues inherent to platelets derived from blood donors - the ability to scale up/down more flexibly according to demand and therefore less precarious supply line, reduction of the risk of exposure to infectious agents and finally the possibility of engineering stem cells to reduce immunogenicity. Here we define the quality control tools and suggest measures for implementation across the field for in vitro platelet genesis, to aid collaboration between laboratories and to aid production of the burdens of proof that will eventually be required by regulators for efficacy and biosafety. We will do this firstly, by addressing the quality control of the nucleated cells used to make the platelets with a particular emphasis to safety issues and secondly, we will look at how platelet function measurement are addressed particularly in the context of platelets derived in vitro.