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Matrix-Assisted Transplantation of Functional Beige Adipose Tissue

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 respiratio...

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Autores principales: Tharp, Kevin M., Jha, Amit K., Kraiczy, Judith, Yesian, Alexandra, Karateev, Grigory, Sinisi, Riccardo, Dubikovskaya, Elena A., Healy, Kevin E., Stahl, Andreas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4613967/
https://www.ncbi.nlm.nih.gov/pubmed/26293504
http://dx.doi.org/10.2337/db15-0728
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author Tharp, Kevin M.
Jha, Amit K.
Kraiczy, Judith
Yesian, Alexandra
Karateev, Grigory
Sinisi, Riccardo
Dubikovskaya, Elena A.
Healy, Kevin E.
Stahl, Andreas
author_facet Tharp, Kevin M.
Jha, Amit K.
Kraiczy, Judith
Yesian, Alexandra
Karateev, Grigory
Sinisi, Riccardo
Dubikovskaya, Elena A.
Healy, Kevin E.
Stahl, Andreas
author_sort Tharp, Kevin M.
collection PubMed
description 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.
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spelling pubmed-46139672016-11-01 Matrix-Assisted Transplantation of Functional Beige Adipose Tissue Tharp, Kevin M. Jha, Amit K. Kraiczy, Judith Yesian, Alexandra Karateev, Grigory Sinisi, Riccardo Dubikovskaya, Elena A. Healy, Kevin E. Stahl, Andreas Diabetes Metabolism 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. American Diabetes Association 2015-11 2015-08-20 /pmc/articles/PMC4613967/ /pubmed/26293504 http://dx.doi.org/10.2337/db15-0728 Text en © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
spellingShingle Metabolism
Tharp, Kevin M.
Jha, Amit K.
Kraiczy, Judith
Yesian, Alexandra
Karateev, Grigory
Sinisi, Riccardo
Dubikovskaya, Elena A.
Healy, Kevin E.
Stahl, Andreas
Matrix-Assisted Transplantation of Functional Beige Adipose Tissue
title Matrix-Assisted Transplantation of Functional Beige Adipose Tissue
title_full Matrix-Assisted Transplantation of Functional Beige Adipose Tissue
title_fullStr Matrix-Assisted Transplantation of Functional Beige Adipose Tissue
title_full_unstemmed Matrix-Assisted Transplantation of Functional Beige Adipose Tissue
title_short Matrix-Assisted Transplantation of Functional Beige Adipose Tissue
title_sort matrix-assisted transplantation of functional beige adipose tissue
topic Metabolism
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4613967/
https://www.ncbi.nlm.nih.gov/pubmed/26293504
http://dx.doi.org/10.2337/db15-0728
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