title: Matrix-Assisted Transplantation of Functional Beige Adipose Tissue.
abstract: Novel, clinically relevant, approaches to shift energy balance are urgently needed to combat metabolic disorders such as obesity and diabetes. One promising approach has been the expansion of brown adipose tissues that express uncoupling protein (UCP) 1 and thus can uncouple mitochondrial respiration from ATP synthesis. While expansion of UCP1-expressing adipose depots may be achieved in rodents via genetic and pharmacological manipulations or the transplantation of brown fat depots, these methods are difficult to use for human clinical intervention. We present a novel cell scaffold technology optimized to establish functional brown fat-like depots in vivo. We adapted the biophysical properties of hyaluronic acid-based hydrogels to support the differentiation of white adipose tissue-derived multipotent stem cells (ADMSCs) into lipid-accumulating, UCP1-expressing beige adipose tissue. Subcutaneous implantation of ADMSCs within optimized hydrogels resulted in the establishment of distinct UCP1-expressing implants that successfully attracted host vasculature and persisted for several weeks. Importantly, implant recipients demonstrated elevated core body temperature during cold challenges, enhanced respiration rates, improved glucose homeostasis, and reduced weight gain, demonstrating the therapeutic merit of this highly translatable approach. This novel approach is the first truly clinically translatable system to unlock the therapeutic potential of brown fat-like tissue expansion.
authors: Graduate Program in Metabolic Biology, Department of Nutritional Sciences & Toxicology, University of California, Berkeley, Berkeley, CA Department of Bioengineering, University of California, Berkeley, Berkeley, CA.
authors: Kevin M
authors: KM
authors: Tharp
authors: Department of Bioengineering, University of California, Berkeley, Berkeley, CA.
authors: Amit K
authors: AK
authors: Jha
authors: Graduate Program in Metabolic Biology, Department of Nutritional Sciences & Toxicology, University of California, Berkeley, Berkeley, CA.
authors: Judith
authors: J
authors: Kraiczy
authors: Graduate Program in Metabolic Biology, Department of Nutritional Sciences & Toxicology, University of California, Berkeley, Berkeley, CA.
authors: Alexandra
authors: A
authors: Yesian
authors: Institute of Chemical Sciences and Engineering, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors: Grigory
authors: G
authors: Karateev
authors: Institute of Chemical Sciences and Engineering, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors: Riccardo
authors: R
authors: Sinisi
authors: Institute of Chemical Sciences and Engineering, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors: Elena A
authors: EA
authors: Dubikovskaya
authors: Department of Bioengineering, University of California, Berkeley, Berkeley, CA Department of Materials Science & Engineering, University of California, Berkeley, Berkeley, CA astahl@berkeley.edu kehealy@berkeley.edu.
authors: Kevin E
authors: KE
authors: Healy
authors: Graduate Program in Metabolic Biology, Department of Nutritional Sciences & Toxicology, University of California, Berkeley, Berkeley, CA astahl@berkeley.edu kehealy@berkeley.edu.
authors: Andreas
authors: A
authors: Stahl
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D002001:Adipose Tissue, Brown / Q000378:metabolism / Q000637:transplantation*; D000818:Animals; D001831:Body Temperature / Q000502:physiology; D002448:Cell Adhesion / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D003080:Cold Temperature; D004734:Energy Metabolism / Q000502:physiology; D007473:Ion Channels / Q000378:metabolism*; D051379:Mice; D024101:Mitochondrial Proteins / Q000378:metabolism*; D013234:Stem Cells / Q000378:metabolism*; D022722:Thermogenesis / Q000502:physiology*; D054457:Tissue Scaffolds; D000071256:Uncoupling Protein 1
chemical_list: D007473:Ion Channels; D024101:Mitochondrial Proteins; C000604371:UCP1 protein, human; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1