Mesenchymal Stem Cell-Derived Exosomes Protect Muscle Loss by miR-145-5p Activity Targeting Activin A Receptors

Skeletal muscle mass is decreased under a wide range of pathologic conditions. In particular, chemotherapy is well known for inducing muscle loss and atrophy. Previous studies using tonsil-derived mesenchymal stem cells (T-MSCs) or a T-MSC-conditioned medium showed effective recovery of total body w...

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Main Authors: Kyung-Ah Cho, Da-Won Choi, Yu-Hee Kim, Jungwoo Kim, Kyung-Ha Ryu, So-Youn Woo
Format: Article
Language:English
Published: MDPI AG 2021-08-01
Series:Cells
Subjects:
Online Access:https://www.mdpi.com/2073-4409/10/8/2169
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author Kyung-Ah Cho
Da-Won Choi
Yu-Hee Kim
Jungwoo Kim
Kyung-Ha Ryu
So-Youn Woo
author_facet Kyung-Ah Cho
Da-Won Choi
Yu-Hee Kim
Jungwoo Kim
Kyung-Ha Ryu
So-Youn Woo
author_sort Kyung-Ah Cho
collection DOAJ
description Skeletal muscle mass is decreased under a wide range of pathologic conditions. In particular, chemotherapy is well known for inducing muscle loss and atrophy. Previous studies using tonsil-derived mesenchymal stem cells (T-MSCs) or a T-MSC-conditioned medium showed effective recovery of total body weight in the chemotherapy-preconditioned bone marrow transplantation mouse model. This study investigated whether extracellular vesicles of T-MSCs, such as exosomes, are a key player in the recovery of body weight and skeletal muscle mass in chemotherapy-treated mice. T-MSC exosomes transplantation significantly decreased loss of total body weight and muscle mass in the busulfan-cyclophosphamide conditioning regimen in BALB/c recipient mice containing elevated serum activin A. Additionally, T-MSC exosomes rescued impaired C2C12 cell differentiation in the presence of activin A in vitro. We found that T-MSC exosomes possess abundant miR-145-5p, which targets activin A receptors, ACVR2A, and ACVR1B. Indeed, T-MSC exosomes rescue muscle atrophy both in vivo and in vitro via miR-145-5p dependent manner. These results suggest that T-MSC exosomes have therapeutic potential to maintain or improve skeletal muscle mass in various activin A elevated pathologic conditions.
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spelling doaj.art-95e896fcc5d240fcb809c4d3c47c92ee2023-11-22T07:12:43ZengMDPI AGCells2073-44092021-08-01108216910.3390/cells10082169Mesenchymal Stem Cell-Derived Exosomes Protect Muscle Loss by miR-145-5p Activity Targeting Activin A ReceptorsKyung-Ah Cho0Da-Won Choi1Yu-Hee Kim2Jungwoo Kim3Kyung-Ha Ryu4So-Youn Woo5Department of Microbiology, College of Medicine, Ewha Womans University, Seoul 07804, KoreaDepartment of Microbiology, College of Medicine, Ewha Womans University, Seoul 07804, KoreaAdvanced Biomedical Research Institute, Ewha Womans University Seoul Hospital, Seoul 07804, KoreaDepartment of Microbiology, College of Medicine, Ewha Womans University, Seoul 07804, KoreaDepartment of Pediatrics, College of Medicine, Ewha Womans University, Seoul 07804, KoreaDepartment of Microbiology, College of Medicine, Ewha Womans University, Seoul 07804, KoreaSkeletal muscle mass is decreased under a wide range of pathologic conditions. In particular, chemotherapy is well known for inducing muscle loss and atrophy. Previous studies using tonsil-derived mesenchymal stem cells (T-MSCs) or a T-MSC-conditioned medium showed effective recovery of total body weight in the chemotherapy-preconditioned bone marrow transplantation mouse model. This study investigated whether extracellular vesicles of T-MSCs, such as exosomes, are a key player in the recovery of body weight and skeletal muscle mass in chemotherapy-treated mice. T-MSC exosomes transplantation significantly decreased loss of total body weight and muscle mass in the busulfan-cyclophosphamide conditioning regimen in BALB/c recipient mice containing elevated serum activin A. Additionally, T-MSC exosomes rescued impaired C2C12 cell differentiation in the presence of activin A in vitro. We found that T-MSC exosomes possess abundant miR-145-5p, which targets activin A receptors, ACVR2A, and ACVR1B. Indeed, T-MSC exosomes rescue muscle atrophy both in vivo and in vitro via miR-145-5p dependent manner. These results suggest that T-MSC exosomes have therapeutic potential to maintain or improve skeletal muscle mass in various activin A elevated pathologic conditions.https://www.mdpi.com/2073-4409/10/8/2169mesenchymal stem cellexosomesskeletal muscleactivin A
spellingShingle Kyung-Ah Cho
Da-Won Choi
Yu-Hee Kim
Jungwoo Kim
Kyung-Ha Ryu
So-Youn Woo
Mesenchymal Stem Cell-Derived Exosomes Protect Muscle Loss by miR-145-5p Activity Targeting Activin A Receptors
Cells
mesenchymal stem cell
exosomes
skeletal muscle
activin A
title Mesenchymal Stem Cell-Derived Exosomes Protect Muscle Loss by miR-145-5p Activity Targeting Activin A Receptors
title_full Mesenchymal Stem Cell-Derived Exosomes Protect Muscle Loss by miR-145-5p Activity Targeting Activin A Receptors
title_fullStr Mesenchymal Stem Cell-Derived Exosomes Protect Muscle Loss by miR-145-5p Activity Targeting Activin A Receptors
title_full_unstemmed Mesenchymal Stem Cell-Derived Exosomes Protect Muscle Loss by miR-145-5p Activity Targeting Activin A Receptors
title_short Mesenchymal Stem Cell-Derived Exosomes Protect Muscle Loss by miR-145-5p Activity Targeting Activin A Receptors
title_sort mesenchymal stem cell derived exosomes protect muscle loss by mir 145 5p activity targeting activin a receptors
topic mesenchymal stem cell
exosomes
skeletal muscle
activin A
url https://www.mdpi.com/2073-4409/10/8/2169
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