SummaryHuman 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.

Over 20 years, Si has been investigated as a promising alternative to conventional graphite because of its high specific capacity and proper working voltage. As numerous strategies have demonstrated their improved electrochemical properties by addressing the intrinsic challenges of Si anode, the practical investigation with a full cell has been regarded as an important task to verify their feasibilities. In this Perspective, we discuss key issues in the practical implementation of the Si anode in the high-energy full cell. With the target of improvement in the volumetric energy density, the comprehensive overview of an electrochemical cell design for Si anodes is presented with its influence on electrochemical properties. Moreover, we highlight the electrode swelling issues and the capacity fading of the Si anode, which is pronounced in the full cell rather than in the half cell. Finally, we offer insights regarding the potential future directions in the development of the Si anode for high-energy lithium-ion batteries.

• Platelet PDI regulates a IIb b 3 integrin activation without affecting platelet activation and inside-out integrin signaling.• Platelet PDI is essential for platelet accumulation but not for fibrin generation and hemostasis in mice.Protein disulfide isomerase (PDI) derived from intravascular cells is required for thrombus formation. However, it remains unclear whether platelet PDI contributes to the process. Using platelet-specific PDI-deficient mice, we demonstrate that PDI-null platelets have defects in aggregation and adenosine triphosphate secretion induced by thrombin, collagen, and adenosine diphosphate. Such defects were rescued by wildtype but not mutant PDI, indicating that the isomerase activity of platelet surface PDI is critical for the regulatory effect. PDI-deficient platelets expressed increased levels of intracellular ER protein 57 (ERp57) and ERp72. Platelet PDI regulated a IIb b 3 integrin activation but not P-selectin exposure, Ca 21 mobilization, b 3 -talin1 interaction, or platelet spreading on immobilized fibrinogen. Inhibition of ERp57 further diminished a IIb b 3 integrin activation and aggregation of activated PDI-deficient platelets, suggesting distinct roles of PDI and ERp57 in platelet functions. We found that platelet PDI is important for thrombus formation on collagen-coated surfaces under shear. Intravital microscopy demonstrates that platelet PDI is important for platelet accumulation but not initial adhesion and fibrin generation following laser-induced arteriolar injury. Tail bleeding time in platelet-specific PDI-deficient mice were not significantly increased. Our results provide important evidence that platelet PDI is essential for thrombus formation but not for hemostasis in mice. (Blood. 2013;122(6):1052-1061 IntroductionPlatelets play a central role in hemostasis and atherothrombosis. Following vascular injury, platelets rapidly adhere to activated endothelial cells and/or subendothelial matrix proteins such as collagen and von Willebrand factor through receptor-ligand interactions.1 Subsequently, activated platelets expose P-selectin from a-granules to the plasma membrane and release other granular molecules such as adenosine diphosphate (ADP), which activates other platelets and facilitates a IIb b 3 integrin-mediated platelet accumulation at the site of vascular injury. Although it is not fully understood how integrin function is regulated, it has been postulated that thiol rearrangement in integrins could be one of the regulatory mechanisms. [2][3][4] Previous studies showed that a IIb b 3 integrin has an endogenous isomerase activity and exposes free sulfhydryl groups during platelet activation. [4][5][6] Consistently, reducing agents such as reduced glutathione and cysteine affect platelet aggregation. 2,7,8 Using a IIb b 3 integrin with mutations on Cys residues, Mor-Cohen et al 9 reported that different disulfide bonds in the b 3 subunit change the structure and function of a IIb b 3 integrin. Moreover, disruption of the disulfide bonds of Cys5-Cys435 or Cys663...