A model niche system to expand platelets for transfusion

对于患有严重血小板减少症或癌症的患者来说，输注血小板可以挽救生命，但同时也有风险

Platelet transfusion can be life-saving for patients with severe thrombocytopenia or cancer but carries the risk of infection and alloimmunization. Nearly 7,000 units of platelets are needed daily, but finding sufficient sources of donor platelets is difficult. Furthermore, the shelf life of donor platelets is limited and transfused units carry the risk of viral or bacterial infection. The development of new techniques to expand platelets in vitro would greatly increase the ability to meet clinical demands, effectively reduce the cost of unit safety testing, significantly enhance transfusion medicine and aid in patient treatment. Numerous iterations of culture conditions have led to modest expansion of platelets, with incomplete functionality. These culture systems predominantly consist of cells seeded on a tissue culture plate with static growth media containing a cocktail of cytokines or small molecules, and thereby embody only a partial representation of the native bone marrow microenvironment. Recently, the addition of shear stress to culture systems has been demonstrated to increase platelet production but this condition alone has not been sufficient to expand platelets to therapeutic levels. Cell signaling in megakaryocyte progenitors through direct or indirect contact with other candidate niche cells has not been fully investigated and may be the key to bringing proplatelet formation and shedding levels to clinical range. Our preliminary results show for the first time that MSCs exist within cord blood (cbMSCs) and share many similarities with those found in the bone marrow. Furthermore, these cells can be co-cultured with cord blood derived megakaryocytes in vitro to enhance platelet formation. Therefore, our overall goal is to develop an optimized model niche system that combines candidate niche cells, shear stress experienced in vivo, and a biomimetic vascular network to foster platelet formation in vitro for patient transplantation. Our first specific aim is to validate the role of MSCs from human CB in enhancing thrombopoiesis in vitro. Our second specific aim is to create a dynamic model niche system to foster platelet formation in vitro. In addition to forming platelets for clinical use, future applications of our system include mechanistic studies investigating platelet dysfunction in patients with genetic diseases, imaging investigations into the process of platelet release in its niche, and the ability to screen therapeutics with human cells.