Menéndez-Pérez Javier, Ajanel Abigail, Campbell Robert A
Department of Emergency Medicine, Washington University School of Medicine, St. Louis, MO, USA.
Curr Opin Hematol. 2025 Jul 14. doi: 10.1097/MOH.0000000000000879.
In this review, we will describe murine models developed to examine human platelet function.
Platelets are critical cells necessary to regulate hemostasis after vessel injury. However, excessive platelet activation can lead to thrombotic complications. Preclinical/translational models are critical in developing therapeutics against platelet activation and to understand mechanistically how platelets function. Researchers have relied on murine models to study platelet function in vivo due to ease of establishing genetic knockouts as well as their lower cost and high throughput nature compared to larger animal models. However, while murine platelets are similar to human based on transcriptomic and proteomic analysis, there are significant differences between the two species, which limits their translation to the human system. To overcome these hurdles, investigators have targeted human platelet genes into the murine genome to express human receptors in mouse platelets. In addition, transfusion models of human platelets into mice have provided valuable insight into human platelet function.
Murine models are a value tool to examine platelet function in hemostasis and thrombosis. Continued focus on developing mouse models where platelets resemble those circulating in humans will offer valuable insight into important pathways, which may be targeted in the future.
在本综述中，我们将描述为研究人类血小板功能而建立的小鼠模型。
血小板是血管损伤后调节止血所必需的关键细胞。然而，血小板过度激活会导致血栓形成并发症。临床前/转化模型对于开发抗血小板激活的治疗方法以及从机制上理解血小板的功能至关重要。由于与大型动物模型相比，建立基因敲除小鼠更容易，成本更低且具有高通量特性，研究人员一直依靠小鼠模型在体内研究血小板功能。然而，尽管基于转录组学和蛋白质组学分析，小鼠血小板与人类血小板相似，但这两个物种之间仍存在显著差异，这限制了它们向人类系统的转化。为了克服这些障碍，研究人员已将人类血小板基因靶向导入小鼠基因组，以便在小鼠血小板中表达人类受体。此外，将人类血小板输注到小鼠体内的模型为了解人类血小板功能提供了有价值的见解。
小鼠模型是研究止血和血栓形成中血小板功能的有价值工具。持续关注开发血小板类似于人类循环血小板的小鼠模型，将为未来可能作为靶点的重要途径提供有价值的见解。
