Search

Your search keyword '"Khalil, Andrew S."' showing total 11 results
Start Over Author "Khalil, Andrew S." Search Limiters Available in Library Collection
11 results on '"Khalil, Andrew S."'

2. Functionalization of microparticles with mineral coatings enhances non-viral transfection of primary human cells.

Author

Khalil, Andrew S, Yu, Xiaohua, Xie, Angela W, Fontana, Gianluca, Umhoefer, Jennifer M, Johnson, Hunter J, Hookway, Tracy A, McDevitt, Todd C, and Murphy, William L

Subjects
Cell Membrane, Fibroblasts, Humans, Fluorides, Minerals, Lipids, DNA, Drug Carriers, Transfection, Microspheres, Transgenes, Nanostructures, Gene Therapy, Stem Cell Research, Biotechnology, Bioengineering, Genetics, 5.2 Cellular and gene therapies, Generic Health Relevance, Biochemistry and Cell Biology, Other Physical Sciences
Abstract

Gene delivery to primary human cells is a technology of critical interest to both life science research and therapeutic applications. However, poor efficiencies in gene transfer and undesirable safety profiles remain key limitations in advancing this technology. Here, we describe a materials-based approach whereby application of a bioresorbable mineral coating improves microparticle-based transfection of plasmid DNA lipoplexes in several primary human cell types. In the presence of these mineral-coated microparticles (MCMs), we observed up to 4-fold increases in transfection efficiency with simultaneous reductions in cytotoxicity. We identified mechanisms by which MCMs improve transfection, as well as coating compositions that improve transfection in three-dimensional cell constructs. The approach afforded efficient transfection in primary human fibroblasts as well as mesenchymal and embryonic stem cells for both two- and three-dimensional transfection strategies. This MCM-based transfection is an advancement in gene delivery technology, as it represents a non-viral approach that enables highly efficient, localized transfection and allows for transfection of three-dimensional cell constructs.

Published
2017

8. Development of a physiological insulin resistance model in human stem cell–derived adipocytes

Author

Massachusetts Institute of Technology. Department of Biology, Friesen, Max, Khalil, Andrew S, Barrasa, M Inmaculada, Jeppesen, Jacob F, Mooney, David J, Jaenisch, Rudolf, Massachusetts Institute of Technology. Department of Biology, Friesen, Max, Khalil, Andrew S, Barrasa, M Inmaculada, Jeppesen, Jacob F, Mooney, David J, and Jaenisch, Rudolf

Abstract

Adipocytes are key regulators of human metabolism, and their dysfunction in insulin signaling is central to metabolic diseases including type II diabetes mellitus (T2D). However, the progression of insulin resistance into T2D is still poorly understood. This limited understanding is due, in part, to the dearth of suitable models of insulin signaling in human adipocytes. Traditionally, adipocyte models fail to recapitulate in vivo insulin signaling, possibly due to exposure to supraphysiological nutrient and hormone conditions. We developed a protocol for human pluripotent stem cell–derived adipocytes that uses physiological nutrient conditions to produce a potent insulin response comparable to in vivo adipocytes. After systematic optimization, this protocol allows robust insulin-stimulated glucose uptake and transcriptional insulin response. Furthermore, exposure of sensitized adipocytes to physiological hyperinsulinemia dampens insulin-stimulated glucose uptake and dysregulates insulin-responsive transcription. Overall, our methodology provides a novel platform for the mechanistic study of insulin signaling and resistance using human pluripotent stem cell–derived adipocytes.

Published
2022

Catalog

Books, media, physical & digital resources
See catalog results