Background: Pluripotent cell-derived islet replacement therapy offers promise for treating Type 1 diabetes (T1D), but concerns about uncontrolled cell proliferation and tumorigenicity present significant safety challenges. To address the safety concern, this study aims to establish a proof-of-concept for a glucose-responsive, insulin-secreting cell line integrated with a built-in FailSafe kill-switch.
Method: We generated β cell-induced progenitor-like cells (βiPLCs) from primary mouse pancreatic β cells through interrupted reprogramming.
This study employs computational chemistry to investigate the detailed mechanisms behind the dissolution of thermally activated clays, which are emerging as promising supplementary cementitious materials (SCM) for enhancing concrete properties and reducing carbon footprint. Specifically, the study employs a first-principles methodology for obtaining activation energies (Δ) involved in the dissolution of metakaolinite (MK) silicate units using NaOH and KOH activators. The investigation includes considerations of hydrolyzing oxo-bridging covalent bonds, van der Waals (vdW) interactions, and the influence of water molecules surrounding alkali cations.
View Article and Find Full Text PDFGeopolymers offer a potential alternative to ordinary Portland cement owing to their performance in mechanical and thermal properties, as well as environmental benefits stemming from a reduced carbon footprint. This paper endeavors to build upon prior atomistic computational work delving deeper into the intricate relationship between pH levels and the resulting material's properties, including pore size distribution, geopolymer nucleate cluster dimensions, total system energy, and monomer poly-condensation behavior. Coarse-grained Monte Carlo (CGMC) simulation inputs include tetrahedral geometry and binding energy parameters derived from DFT simulations for aluminate and silicate monomers.
View Article and Find Full Text PDFThe immunogenicity of transplanted allogeneic cells and tissues is a major hurdle to the advancement of cell therapies. Here we show that the overexpression of eight immunomodulatory transgenes (Pdl1, Cd200, Cd47, H2-M3, Fasl, Serpinb9, Ccl21 and Mfge8) in mouse embryonic stem cells (mESCs) is sufficient to immunologically 'cloak' the cells as well as tissues derived from them, allowing their survival for months in outbred and allogeneic inbred recipients. Overexpression of the human orthologues of these genes in human ESCs abolished the activation of allogeneic human peripheral blood mononuclear cells and their inflammatory responses.
View Article and Find Full Text PDFHuman induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (hiPSC-CMs) hold tremendous potential for cardiovascular disease modeling, drug screening, personalized medicine, and pathophysiology studies. The availability of a robust protocol and functional assay for studying phenotypic behavior of hiPSC-CMs is essential for establishing an in vitro disease model. Many heart diseases manifest due to changes in the mechanical strain of cardiac tissue.
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