Cardiovascular progenitor cells (CVPCs) derived from human pluripotent stem cells (hPSCs), including human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs), hold great promise for the study of cardiovascular development and cell-based therapy of heart diseases, but their applications are challenged by the difficulties in their efficient generation and stable maintenance. This study aims to develop chemically defined systems for robust generation and stable propagation of hPSC-derived CVPCs by modulating the key early developmental pathways involved in human cardiovascular specification and CVPC self-renewal. Herein we report that a combination of bone morphogenetic protein 4 (BMP4), glycogen synthase kinase 3 (GSK3) inhibitor CHIR99021 and ascorbic acid is sufficient to rapidly convert monolayer-cultured hPSCs, including hESCs and hiPSCs, into homogeneous CVPCs in a chemically defined medium under feeder-and serum-free culture conditions. These CVPCs stably self-renewed under feeder-and serum-free conditions and expanded over 10 7 -fold when the differentiation-inducing signals from BMP, GSK3 and Activin/Nodal pathways were simultaneously eliminated. Furthermore, these CVPCs exhibited expected genome-wide molecular features of CVPCs, retained potentials to generate major cardiovascular lineages including cardiomyocytes, smooth muscle cells and endothelial cells in vitro, and were non-tumorigenic in vivo. Altogether, the established systems reported here permit efficient generation and stable maintenance of hPSCderived CVPCs, which represent a powerful tool to study early embryonic cardiovascular development and provide a potentially safe source of cells for myocardial regenerative medicine.

This is the largest study of hPSCs in nonhuman primates in cardiovascular field to date (n=32). Compared with cyclosporine alone, MDR attenuates immune rejection and improves survival of hPSC-CVPCs in primates; this is associated with less apoptosis of native cardiac cells and better recovery of left ventricular function at 28 days. However, even with MDR, transplanted hPSC-CVPCs do not engraft and do not survive at 140 days after transplantation, thereby excluding remuscularization as a mechanism for the functional effect.

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Supercapacitors based on nanoporous carbon materials, commonly called electric double-layer capacitors (EDLCs), have recently attracted considerable attention. [1,2] Carbon supercapacitors bridge the gap between batteries and conventional dielectric capacitors, and are ideal for the rapid storage and release of energy. To develop supercapacitors as an alternative to batteries, currently intense research efforts aim at increasing the energy density by optimizing the pore size distribution of nanoporous carbon materials. In their breakthrough work, Gogotsi and co-workers [3] synthesized carbidederived carbons with unimodal micropores [4] smaller than 1 nm, and found that these new materials exhibit an anomalous increase in capacitance compared to others with pore sizes above 2 nm. These results challenge the long-held presumption that pores smaller than the size of solvated electrolyte ions do not contribute to energy storage. Herein, we present an explanation for the anomalous increase in capacitance for pores below 1 nm and for the slightly increasing capacitance with increasing pore size above 2 nm by using a heuristic theoretical model and first-principles density functional theory (DFT) calculations.Generally it is assumed that the capacitance of EDLCs follows that of a parallel-plate capacitor:where e r is the electrolyte dielectric constant, e 0 is the permittivity of a vacuum, A is the electrode specific surface area, and d is the effective thickness of the electric double layer (the Debye length). Assuming a planar pore surface, Gogotsi and co-workers [3] found that the normalized capacitance of the micropores (C/A) is proportional to the reciprocal radius of the micropores (1/d).[5] This finding appears to be in good agreement with Equation (1), showing the dominance of the 1/d term compared to the pore curvature. However, a close inspection reveals that the intercept of the linear fit is not zero (see Figure S1 in the Supporting Information). There is still a lack of a good model for nanoporous carbon supercapacitors. What happens inside the nanoconfined space within the pores is not fully understood; the effects of pore size distribution, A, and d on C are still not clear. [6][7][8] Moving beyond the planar capacitor model, it seems reasonable to include the influence of pore curvature to describe the capacitance of carbon supercapacitors. Nanoporous materials can have various pore shapes, such as cylindrical, slit, and spherical types.[9] Mesoporous carbon materials obtained by template methods usually have wormhole structures. [6,10] Cylindrical pores are usually the assumption for theoretical treatments for physical adsorption of gases [11] and impedance spectroscopy. [12] Assuming cylindrical mesopores, solvated counterions enter pores and approach the pore walls to form electric double-cylinder capacitors (EDCCs; Figure 1 a). The double-cylinder capacitance is given as:where L is the pore length and b and a are the radii of the outer and inner cylinders, respectively. For micropores, however, the s...

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