Feng, QiangShabrani, NamrataThon, Jonathan N.Huo, HongguangThiel, AustinMachlus, Kellie R.Kim, KyunghoBrooks, JulieLi, FengLuo, ChenmeiKimbrel, Erin A.Wang, JiwuKim, Kwang-SooItaliano, JosephCho, JaehyungLu, Shi-JiangLanza, Robert2014-12-022014Feng, Q., N. Shabrani, J. Thon, H. Huo, A. Thiel, K. Machlus, K. Kim, et al. 2014. “Scalable Generation of Universal Platelets from Human Induced Pluripotent Stem Cells.” Stem Cell Reports 3 (5): 817-831. doi:10.1016/j.stemcr.2014.09.010. http://dx.doi.org/10.1016/j.stemcr.2014.09.010.2213-6711http://nrs.harvard.edu/urn-3:HUL.InstRepos:13454781Summary Human induced pluripotent stem cells (iPSCs) provide a potentially replenishable source for the production of transfusable platelets. Here, we describe a method to generate megakaryocytes (MKs) and functional platelets from iPSCs in a scalable manner under serum/feeder-free conditions. The method also permits the cryopreservation of MK progenitors, enabling a rapid “surge” capacity when large numbers of platelets are needed. Ultrastructural/morphological analyses show no major differences between iPSC platelets and human blood platelets. iPSC platelets form aggregates, lamellipodia, and filopodia after activation and circulate in macrophage-depleted animals and incorporate into developing mouse thrombi in a manner identical to human platelets. By knocking out the β2-microglobulin gene, we have generated platelets that are negative for the major histocompatibility antigens. The scalable generation of HLA-ABC-negative platelets from a renewable cell source represents an important step toward generating universal platelets for transfusion as well as a potential strategy for the management of platelet refractoriness.en-USJournal Article2014-12-0210.1016/j.stemcr.2014.09.010