Losartan Improves Adipose Tissue-Derived Stem Cell Niche by Inhibiting Transforming Growth Factor-β and Fibrosis in Skeletal Muscle Injury

Recently, adipose tissue-derived stem cells (ASCs) were emerged as an alternative, abundant, and easily accessible source of stem cell therapy. Previous studies revealed losartan (an angiotensin II type I receptor blocker) treatment promoted the healing of skeletal muscle by attenuation of the TGF-β...

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Main Authors: Jin-Kyu Park, Mi-Ran Ki, Eun-Mi Lee, Ah-Young Kim, Sang-Young You, Seon-Young Han, Eun-Joo Lee, Il-Hwa Hong, Soon-Hak Kwon, Seong-Jin Kim, Thomas A. Rando, Kyu-Shik Jeong D.V.M., Ph.D.
Format: Article
Language:English
Published: SAGE Publishing 2012-11-01
Series:Cell Transplantation
Online Access:https://doi.org/10.3727/096368912X637055
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author Jin-Kyu Park
Mi-Ran Ki
Eun-Mi Lee
Ah-Young Kim
Sang-Young You
Seon-Young Han
Eun-Joo Lee
Il-Hwa Hong
Soon-Hak Kwon
Seong-Jin Kim
Thomas A. Rando
Kyu-Shik Jeong D.V.M., Ph.D.
author_facet Jin-Kyu Park
Mi-Ran Ki
Eun-Mi Lee
Ah-Young Kim
Sang-Young You
Seon-Young Han
Eun-Joo Lee
Il-Hwa Hong
Soon-Hak Kwon
Seong-Jin Kim
Thomas A. Rando
Kyu-Shik Jeong D.V.M., Ph.D.
author_sort Jin-Kyu Park
collection DOAJ
description Recently, adipose tissue-derived stem cells (ASCs) were emerged as an alternative, abundant, and easily accessible source of stem cell therapy. Previous studies revealed losartan (an angiotensin II type I receptor blocker) treatment promoted the healing of skeletal muscle by attenuation of the TGF-β signaling pathway, which inhibits muscle differentiation. Therefore, we hypothesized that a combined therapy using ASCs and losartan might dramatically improve the muscle remodeling after muscle injury. To determine the combined effect of losartan with ASC transplantation, we created a muscle laceration mouse model. EGFP-labeled ASCs were locally transplanted to the injured gastrocnemius muscle after muscle laceration. The dramatic muscle regeneration and the remarkably inhibited muscular fibrosis were observed by combined treatment. Transplanted ASCs fused with the injured or differentiating myofibers. Myotube formation was also enhanced by ASC + satellite coculture and losartan treatment. Thus, the present study indicated that ASC transplantation effect for skeletal muscle injury can be dramatically improved by losartan treatment inducing better niche.
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spelling doaj.art-59c824f2c14c4a1e9a628f8591c1a24c2022-12-21T23:54:14ZengSAGE PublishingCell Transplantation0963-68971555-38922012-11-012110.3727/096368912X637055Losartan Improves Adipose Tissue-Derived Stem Cell Niche by Inhibiting Transforming Growth Factor-β and Fibrosis in Skeletal Muscle InjuryJin-Kyu Park0Mi-Ran Ki1Eun-Mi Lee2Ah-Young Kim3Sang-Young You4Seon-Young Han5Eun-Joo Lee6Il-Hwa Hong7Soon-Hak Kwon8Seong-Jin Kim9Thomas A. Rando10Kyu-Shik Jeong D.V.M., Ph.D.11College of Veterinary Medicine, Kyungpook National University, Daegu, South KoreaCollege of Veterinary Medicine, Kyungpook National University, Daegu, South KoreaStem Cell Therapeutic Research Institute, Kyungpook National University, Daegu, South KoreaStem Cell Therapeutic Research Institute, Kyungpook National University, Daegu, South KoreaStem Cell Therapeutic Research Institute, Kyungpook National University, Daegu, South KoreaStem Cell Therapeutic Research Institute, Kyungpook National University, Daegu, South KoreaStem Cell Therapeutic Research Institute, Kyungpook National University, Daegu, South KoreaCollege of Veterinary Medicine, Kyungpook National University, Daegu, South KoreaDepartment of Pediatrics, School of Medicine, Kyungpook National University, Daegu, South KoreaCHA Cancer Institute, CHA University, Seoul, South KoreaDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USAStem Cell Therapeutic Research Institute, Kyungpook National University, Daegu, South KoreaRecently, adipose tissue-derived stem cells (ASCs) were emerged as an alternative, abundant, and easily accessible source of stem cell therapy. Previous studies revealed losartan (an angiotensin II type I receptor blocker) treatment promoted the healing of skeletal muscle by attenuation of the TGF-β signaling pathway, which inhibits muscle differentiation. Therefore, we hypothesized that a combined therapy using ASCs and losartan might dramatically improve the muscle remodeling after muscle injury. To determine the combined effect of losartan with ASC transplantation, we created a muscle laceration mouse model. EGFP-labeled ASCs were locally transplanted to the injured gastrocnemius muscle after muscle laceration. The dramatic muscle regeneration and the remarkably inhibited muscular fibrosis were observed by combined treatment. Transplanted ASCs fused with the injured or differentiating myofibers. Myotube formation was also enhanced by ASC + satellite coculture and losartan treatment. Thus, the present study indicated that ASC transplantation effect for skeletal muscle injury can be dramatically improved by losartan treatment inducing better niche.https://doi.org/10.3727/096368912X637055
spellingShingle Jin-Kyu Park
Mi-Ran Ki
Eun-Mi Lee
Ah-Young Kim
Sang-Young You
Seon-Young Han
Eun-Joo Lee
Il-Hwa Hong
Soon-Hak Kwon
Seong-Jin Kim
Thomas A. Rando
Kyu-Shik Jeong D.V.M., Ph.D.
Losartan Improves Adipose Tissue-Derived Stem Cell Niche by Inhibiting Transforming Growth Factor-β and Fibrosis in Skeletal Muscle Injury
Cell Transplantation
title Losartan Improves Adipose Tissue-Derived Stem Cell Niche by Inhibiting Transforming Growth Factor-β and Fibrosis in Skeletal Muscle Injury
title_full Losartan Improves Adipose Tissue-Derived Stem Cell Niche by Inhibiting Transforming Growth Factor-β and Fibrosis in Skeletal Muscle Injury
title_fullStr Losartan Improves Adipose Tissue-Derived Stem Cell Niche by Inhibiting Transforming Growth Factor-β and Fibrosis in Skeletal Muscle Injury
title_full_unstemmed Losartan Improves Adipose Tissue-Derived Stem Cell Niche by Inhibiting Transforming Growth Factor-β and Fibrosis in Skeletal Muscle Injury
title_short Losartan Improves Adipose Tissue-Derived Stem Cell Niche by Inhibiting Transforming Growth Factor-β and Fibrosis in Skeletal Muscle Injury
title_sort losartan improves adipose tissue derived stem cell niche by inhibiting transforming growth factor β and fibrosis in skeletal muscle injury
url https://doi.org/10.3727/096368912X637055
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