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Injectable Allograft Adipose Matrix Supports Adipogenic Tissue Remodeling in the Nude Mouse and Human

BACKGROUND: Adipose tissue reaches cellular stasis after puberty, leaving adipocytes unable to significantly expand or renew under normal physiologic conditions. This is problematic in progressive lipodystrophies, in instances of scarring, and in soft-tissue damage resulting from lumpectomy and trau...

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Autores principales: Kokai, Lauren E., Schilling, Benjamin K., Chnari, Evangelia, Huang, Yen-Chen, Imming, Emily A., Karunamurthy, Arivarasan, Khouri, Roger K., D’Amico, Richard A., Coleman, Sydney R., Marra, Kacey G., Rubin, J. Peter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6358185/
https://www.ncbi.nlm.nih.gov/pubmed/30688888
http://dx.doi.org/10.1097/PRS.0000000000005269
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author Kokai, Lauren E.
Schilling, Benjamin K.
Chnari, Evangelia
Huang, Yen-Chen
Imming, Emily A.
Karunamurthy, Arivarasan
Khouri, Roger K.
D’Amico, Richard A.
Coleman, Sydney R.
Marra, Kacey G.
Rubin, J. Peter
author_facet Kokai, Lauren E.
Schilling, Benjamin K.
Chnari, Evangelia
Huang, Yen-Chen
Imming, Emily A.
Karunamurthy, Arivarasan
Khouri, Roger K.
D’Amico, Richard A.
Coleman, Sydney R.
Marra, Kacey G.
Rubin, J. Peter
author_sort Kokai, Lauren E.
collection PubMed
description BACKGROUND: Adipose tissue reaches cellular stasis after puberty, leaving adipocytes unable to significantly expand or renew under normal physiologic conditions. This is problematic in progressive lipodystrophies, in instances of scarring, and in soft-tissue damage resulting from lumpectomy and traumatic deformities, because adipose tissue will not self-renew once damaged. This yields significant clinical necessity for an off-the-shelf de novo soft-tissue replacement mechanism. METHODS: A process comprising separate steps of removing lipid and cellular materials from adipose tissue has been developed, creating an ambient temperature-stable allograft adipose matrix. Growth factors and matrix proteins relevant to angiogenesis and adipogenesis were identified by enzyme-linked immunosorbent assay and immunohistochemistry, and subcutaneous soft-tissue integration of the allograft adipose matrix was investigated in vivo in both the athymic mouse and the dorsum of the human wrist. RESULTS: Allograft adipose matrix maintained structural components and endogenous growth factors. In vitro, adipose-derived stem cells cultured on allograft adipose matrix underwent adipogenesis in the absence of media-based cues. In vivo, animal modeling showed vasculature formation followed by perilipin A–positive tissue segments. Allograft adipose matrix maintained soft-tissue volume in the dorsal wrist in a 4-month investigation with no severe adverse events, becoming palpably consistent with subcutaneous adipose. CONCLUSIONS: Subcutaneous implantation of allograft adipose matrix laden with retained angiogenic and adipogenic factors served as an inductive scaffold for sustaining adipogenesis. Tissue incorporation assessed histologically from both the subcutaneous injection site of the athymic nude mouse over 6 months and human dorsal wrist presented adipocyte morphology residing within the injected scaffold.
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spelling pubmed-63581852019-02-20 Injectable Allograft Adipose Matrix Supports Adipogenic Tissue Remodeling in the Nude Mouse and Human Kokai, Lauren E. Schilling, Benjamin K. Chnari, Evangelia Huang, Yen-Chen Imming, Emily A. Karunamurthy, Arivarasan Khouri, Roger K. D’Amico, Richard A. Coleman, Sydney R. Marra, Kacey G. Rubin, J. Peter Plast Reconstr Surg Experimental BACKGROUND: Adipose tissue reaches cellular stasis after puberty, leaving adipocytes unable to significantly expand or renew under normal physiologic conditions. This is problematic in progressive lipodystrophies, in instances of scarring, and in soft-tissue damage resulting from lumpectomy and traumatic deformities, because adipose tissue will not self-renew once damaged. This yields significant clinical necessity for an off-the-shelf de novo soft-tissue replacement mechanism. METHODS: A process comprising separate steps of removing lipid and cellular materials from adipose tissue has been developed, creating an ambient temperature-stable allograft adipose matrix. Growth factors and matrix proteins relevant to angiogenesis and adipogenesis were identified by enzyme-linked immunosorbent assay and immunohistochemistry, and subcutaneous soft-tissue integration of the allograft adipose matrix was investigated in vivo in both the athymic mouse and the dorsum of the human wrist. RESULTS: Allograft adipose matrix maintained structural components and endogenous growth factors. In vitro, adipose-derived stem cells cultured on allograft adipose matrix underwent adipogenesis in the absence of media-based cues. In vivo, animal modeling showed vasculature formation followed by perilipin A–positive tissue segments. Allograft adipose matrix maintained soft-tissue volume in the dorsal wrist in a 4-month investigation with no severe adverse events, becoming palpably consistent with subcutaneous adipose. CONCLUSIONS: Subcutaneous implantation of allograft adipose matrix laden with retained angiogenic and adipogenic factors served as an inductive scaffold for sustaining adipogenesis. Tissue incorporation assessed histologically from both the subcutaneous injection site of the athymic nude mouse over 6 months and human dorsal wrist presented adipocyte morphology residing within the injected scaffold. Lippincott Williams & Wilkins 2019-02 2019-01-29 /pmc/articles/PMC6358185/ /pubmed/30688888 http://dx.doi.org/10.1097/PRS.0000000000005269 Text en Copyright © 2019 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Plastic Surgeons. All rights reserved. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND) (http://creativecommons.org/licenses/by-nc-nd/4.0/) , where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
spellingShingle Experimental
Kokai, Lauren E.
Schilling, Benjamin K.
Chnari, Evangelia
Huang, Yen-Chen
Imming, Emily A.
Karunamurthy, Arivarasan
Khouri, Roger K.
D’Amico, Richard A.
Coleman, Sydney R.
Marra, Kacey G.
Rubin, J. Peter
Injectable Allograft Adipose Matrix Supports Adipogenic Tissue Remodeling in the Nude Mouse and Human
title Injectable Allograft Adipose Matrix Supports Adipogenic Tissue Remodeling in the Nude Mouse and Human
title_full Injectable Allograft Adipose Matrix Supports Adipogenic Tissue Remodeling in the Nude Mouse and Human
title_fullStr Injectable Allograft Adipose Matrix Supports Adipogenic Tissue Remodeling in the Nude Mouse and Human
title_full_unstemmed Injectable Allograft Adipose Matrix Supports Adipogenic Tissue Remodeling in the Nude Mouse and Human
title_short Injectable Allograft Adipose Matrix Supports Adipogenic Tissue Remodeling in the Nude Mouse and Human
title_sort injectable allograft adipose matrix supports adipogenic tissue remodeling in the nude mouse and human
topic Experimental
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6358185/
https://www.ncbi.nlm.nih.gov/pubmed/30688888
http://dx.doi.org/10.1097/PRS.0000000000005269
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