Nanyan Zhang, Peter J Newman
Anti-platelet allo-, auto-, and iso-antibodies, which target platelet surface glycoproteins, play a crucial role in immune-mediated platelet destruction across various clinical scenarios. Whole cell platelet assays-while effective in maintaining the conformation of the offending antigen-are limited in characterizing anti-platelet antibodies due to their lack of specificity. Here, we describe a novel strategy for generating bioengineered HLA class I-negative, "antigen-specific" megakaryocytes (MKs) from induced pluripotent stem cells (iPSCs). These engineered cells can be cryopreserved for later distribution and analysis. Combining bioengineered megakaryocytes with flow cytometry allows for rapid detection and characterization of platelet-specific antibodies present in patient plasma. The enhanced sensitivity and remarkable specificity of this approach hold great promise for diagnosing a variety of immune platelet disorders.