Designer fat cells: adipogenic differentiation of CRISPR-Cas9 genome-engineered induced pluripotent stem cells
Year: 2023
Type: article
Abstract: Adipose tissue is an active endocrine organ that can signal bidirectionally to many tissues and organ systems in the body. With obesity, adipose tissue is a source of low-level inflammation that contributes to various co-morbidities and damage to downstream effector tissues. The ability to synthesize genetically engineered adipose tissue could have critical applications in studying adipokine signaling and the use of adipose tissue for novel therapeutic strategies. This study aimed to develop a method for non-viral adipogenic differentiation of genome-edited murine induced pluripotent stem cells (iPSCs) and to test the ability of such cells to engraft in mice in vivo . Designer adipocytes were created from iPSCs, which can be readily genetically engineered using CRISPR-Cas9 to knock out or insert individual genes of interest. As a model system for adipocyte-based drug delivery, an existing iPSC cell line that transcribes interleukin 1 receptor antagonist under the endogenous macrophage chemoattractant protein-1 promoter was tested for adipogenic capabilities under these same differentiation conditions. To understand the role of various adipocyte subtypes and their impact on health and disease, an efficient method was devised for inducing browning and whitening of IPSC-derived adipocytes in culture. Finally, to study the downstream effects of designer adipocytes in vivo , we transplanted the designer adipocytes into fat-free lipodystrophic mice as a model system for studying adipose signaling in different models of disease or repair. This novel translational tissue engineering and regenerative medicine platform provides an innovative approach to studying the role of adipose interorgan communication in various conditions.
Source: European Cells and Materials
DOI: 10.22203/ecm.v046a09
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $1,000
Funders: Washington University in St. Louis, Institute of Clinical and Translational Sciences, Shriners Hospitals for Children, National Institutes of Health, National Institute on Aging, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Arthritis and Musculoskeletal and Skin Diseases
Awards: G1699998815, G2366089456, The Role of Fat in Osteoarthritis, Imaging, Modeling and Engineering of Diabetic Tissues, Obesity, Biomechanics, and Inflammation in Osteoarthritis, Core Center for Musculoskeletal Biology and Medicine, G5330480267, G5588909404, Deconstructing Cartilage Mechanotransduction by Piezo Channels, Viscoelastic Properties of Normal and OA Chondrons, G7008996325, G8840517274, G9000074605, G9000217772, G9000308115, The Multiscale Role of Piezo Channels in Obesity-Associated Cartilage Damage, Washington University Nutrition Obesity Research Center, Washington University Rheumatic Diseases Research Resource-based Center, The Role of Fat in Osteoarthritis, Genetically-engineered stem cells for self-regulating arthritis therapy, RESOURCE BASED CENTER FOR MUSCULOSKELETAL BIOLOGY AND MEDICINE
OpenAlex ID: W4390502132