Gollomp Kandace, Lambert Michele P, Poncz Mortimer
Division of Hematology, Children's Hospital of Philadelphia and the Department of Pediatrics, Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
Curr Opin Hematol. 2017 Nov;24(6):565-571. doi: 10.1097/MOH.0000000000000378.
Donor-derived platelets have proven to be of hemostatic value in many clinical settings. There is a fear that the need for platelets may outgrow the donor pool in first-world countries. Moreover, there are other challenges with donor platelets that add to the impetus to find an alternative platelet source, especially after the megakaryocyte cytokine thrombopoietin was identified. Megakaryocytes have since been differentiated from numerous cell sources and the observed released platelet-like particles (PLPs) have led to calls to develop such products for clinical use. The development of megakaryocytes from embryonic stem cell also supported the concept of developing nondonor-based platelets.
Several groups have claimed that nondonor-based platelets derived from in-vitro grown megakaryocytes may soon become available to supplement or replace donor-derived products, but their number and quality has been wanting. A possible alternative of directly infusing megakaryocytes that release platelets in the lungs - similar to that recently shown for endogenous megakaryocytes - has been proposed.
This present review will describe the present state-of-the-art in generating and delivering nondonor-derived platelets. Progress has been slow, but advances in our ability to generate human megakaryocytes in culture, generate PLPs from these cells, and test the functionality of the resultant platelets in vitro and in vivo have identified important remaining challenges and raised alternative potential solutions.
在许多临床情况下,供体来源的血小板已被证明具有止血价值。人们担心在发达国家对血小板的需求可能会超过供体库。此外,供体血小板还有其他挑战,这增加了寻找替代血小板来源的动力,尤其是在巨核细胞细胞因子血小板生成素被发现之后。此后,巨核细胞已从多种细胞来源分化而来,观察到的释放的血小板样颗粒(PLP)促使人们呼吁开发此类产品用于临床。从胚胎干细胞发育巨核细胞也支持了开发非供体来源血小板的概念。
几个研究小组声称,源自体外培养的巨核细胞的非供体来源血小板可能很快就会用于补充或替代供体来源的产品,但其数量和质量一直不尽人意。有人提出了一种可能的替代方法,即直接输注在肺部释放血小板的巨核细胞,类似于最近对内源性巨核细胞的研究结果。
本综述将描述生成和输送非供体来源血小板的当前技术水平。进展一直很缓慢,但我们在体外培养人类巨核细胞、从这些细胞生成PLP以及在体外和体内测试所得血小板功能方面的能力取得了进展,这已经确定了重要的剩余挑战并提出了潜在的替代解决方案。