Islam Farhana, Javdan Shwan B, Lewis Mitchell R, Craig James D, Wu Han, Deans Tara L
Department of Biomedical Engineering, University of Utah, Salt Lake City, UT 84112, USA.
Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332, USA.
bioRxiv. 2025 Jan 27:2023.10.13.562311. doi: 10.1101/2023.10.13.562311.
Platelets are anucleate cells naturally filled with secretory granules that store large amounts of protein to be released in response to certain physiological conditions. Cell engineering can endow platelets with the ability to deliver non-native proteins by modifying them as they develop during the cell fate process. This study presents a strategy to efficiently generate mouse platelets from pluripotent stem cells and demonstrates their potential as bioengineered protein delivery platforms. By modifying megakaryocytes, the progenitor cells of platelets, we successfully engineered platelets capable of packaging and delivering non-native proteins. These engineered platelets can offer flexible delivery platforms to release non-native proteins in a controlled manner upon activation when packaged into α-granules or deliver active enzymes to genetically alter recipient cells. Our findings highlight platelets as a promising tool for protein delivery in cell therapy applications.
血小板是无核细胞，天然充满分泌颗粒，这些颗粒储存大量蛋白质，可在特定生理条件下释放。细胞工程可以通过在细胞命运过程中对血小板进行修饰，赋予其递送非天然蛋白质的能力。本研究提出了一种从多能干细胞高效生成小鼠血小板的策略，并证明了它们作为生物工程蛋白质递送平台的潜力。通过修饰血小板的祖细胞巨核细胞，我们成功构建了能够包装和递送非天然蛋白质的血小板。这些工程化血小板可以提供灵活的递送平台，当包装到α颗粒中时，在激活后以可控方式释放非天然蛋白质，或者递送活性酶以基因改造受体细胞。我们的研究结果突出了血小板作为细胞治疗应用中蛋白质递送的一种有前景的工具。
