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Direct Conversion of Human Fibroblasts into Adipocytes Using a Novel Small Molecular Compound: Implications for Regenerative Therapy for Adipose Tissue Defects

There is a need in plastic surgery to prepare autologous adipocytes that can be transplanted in patients to reconstruct soft tissue defects caused by tumor resection, including breast cancer, and by trauma and other diseases. Direct conversion of somatic cells into adipocytes may allow sufficient fu...

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Autores principales: Sowa, Yoshihiro, Kishida, Tsunao, Louis, Fiona, Sawai, Seiji, Seki, Makoto, Numajiri, Toshiaki, Takahashi, Kenji, Mazda, Osam
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000077/
https://www.ncbi.nlm.nih.gov/pubmed/33803331
http://dx.doi.org/10.3390/cells10030605
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author Sowa, Yoshihiro
Kishida, Tsunao
Louis, Fiona
Sawai, Seiji
Seki, Makoto
Numajiri, Toshiaki
Takahashi, Kenji
Mazda, Osam
author_facet Sowa, Yoshihiro
Kishida, Tsunao
Louis, Fiona
Sawai, Seiji
Seki, Makoto
Numajiri, Toshiaki
Takahashi, Kenji
Mazda, Osam
author_sort Sowa, Yoshihiro
collection PubMed
description There is a need in plastic surgery to prepare autologous adipocytes that can be transplanted in patients to reconstruct soft tissue defects caused by tumor resection, including breast cancer, and by trauma and other diseases. Direct conversion of somatic cells into adipocytes may allow sufficient functional adipocytes to be obtained for use in regeneration therapy. Chemical libraries of 10,800 molecules were screened for the ability to induce lipid accumulation in human dermal fibroblasts (HDFs) in culture. Chemical compound-mediated directly converted adipocytes (CCCAs) were characterized by lipid staining, immunostaining, and qRT-PCR, and were also tested for adipokine secretion and glucose uptake. CCCAs were also implanted into mice to examine their distribution in vivo. STK287794 was identified as a small molecule that induced the accumulation of lipid droplets in HDFs. CCCAs expressed adipocyte-related genes, secreted adiponectin and leptin, and abundantly incorporated glucose. After implantation in mice, CCCAs resided in granulation tissue and remained adipose-like. HDFs were successfully converted into adipocytes by adding a single chemical compound, STK287794. C/EBPα and PPARγ were upregulated in STK287794-treated cells, which strongly suggests involvement of these adipocyte-related transcription factors in the chemical direct conversion. Our method may be useful for the preparation of autogenous adipocytes for transplantation therapy for soft tissue defects and fat tissue atrophy.
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spelling pubmed-80000772021-03-28 Direct Conversion of Human Fibroblasts into Adipocytes Using a Novel Small Molecular Compound: Implications for Regenerative Therapy for Adipose Tissue Defects Sowa, Yoshihiro Kishida, Tsunao Louis, Fiona Sawai, Seiji Seki, Makoto Numajiri, Toshiaki Takahashi, Kenji Mazda, Osam Cells Article There is a need in plastic surgery to prepare autologous adipocytes that can be transplanted in patients to reconstruct soft tissue defects caused by tumor resection, including breast cancer, and by trauma and other diseases. Direct conversion of somatic cells into adipocytes may allow sufficient functional adipocytes to be obtained for use in regeneration therapy. Chemical libraries of 10,800 molecules were screened for the ability to induce lipid accumulation in human dermal fibroblasts (HDFs) in culture. Chemical compound-mediated directly converted adipocytes (CCCAs) were characterized by lipid staining, immunostaining, and qRT-PCR, and were also tested for adipokine secretion and glucose uptake. CCCAs were also implanted into mice to examine their distribution in vivo. STK287794 was identified as a small molecule that induced the accumulation of lipid droplets in HDFs. CCCAs expressed adipocyte-related genes, secreted adiponectin and leptin, and abundantly incorporated glucose. After implantation in mice, CCCAs resided in granulation tissue and remained adipose-like. HDFs were successfully converted into adipocytes by adding a single chemical compound, STK287794. C/EBPα and PPARγ were upregulated in STK287794-treated cells, which strongly suggests involvement of these adipocyte-related transcription factors in the chemical direct conversion. Our method may be useful for the preparation of autogenous adipocytes for transplantation therapy for soft tissue defects and fat tissue atrophy. MDPI 2021-03-09 /pmc/articles/PMC8000077/ /pubmed/33803331 http://dx.doi.org/10.3390/cells10030605 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ).
spellingShingle Article
Sowa, Yoshihiro
Kishida, Tsunao
Louis, Fiona
Sawai, Seiji
Seki, Makoto
Numajiri, Toshiaki
Takahashi, Kenji
Mazda, Osam
Direct Conversion of Human Fibroblasts into Adipocytes Using a Novel Small Molecular Compound: Implications for Regenerative Therapy for Adipose Tissue Defects
title Direct Conversion of Human Fibroblasts into Adipocytes Using a Novel Small Molecular Compound: Implications for Regenerative Therapy for Adipose Tissue Defects
title_full Direct Conversion of Human Fibroblasts into Adipocytes Using a Novel Small Molecular Compound: Implications for Regenerative Therapy for Adipose Tissue Defects
title_fullStr Direct Conversion of Human Fibroblasts into Adipocytes Using a Novel Small Molecular Compound: Implications for Regenerative Therapy for Adipose Tissue Defects
title_full_unstemmed Direct Conversion of Human Fibroblasts into Adipocytes Using a Novel Small Molecular Compound: Implications for Regenerative Therapy for Adipose Tissue Defects
title_short Direct Conversion of Human Fibroblasts into Adipocytes Using a Novel Small Molecular Compound: Implications for Regenerative Therapy for Adipose Tissue Defects
title_sort direct conversion of human fibroblasts into adipocytes using a novel small molecular compound: implications for regenerative therapy for adipose tissue defects
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000077/
https://www.ncbi.nlm.nih.gov/pubmed/33803331
http://dx.doi.org/10.3390/cells10030605
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