Mesenchymal stem cells and extracellular matrix scaffold promote muscle regeneration by synergistically regulating macrophage polarization toward the M2 phenotype

Abstract Background Skeletal muscle plays an important role in the body’s physiology but there are still no effective treatments for volumetric muscle loss (VML) resulting from severe traumatic injury or tumor excision. Recent studies show that a tissue engineering strategy using a compound containi...

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Main Authors: Xinyu Qiu, Shiyu Liu, Hao Zhang, Bin Zhu, Yuting Su, Chenxi Zheng, Rong Tian, Miao Wang, Huijuan Kuang, Xinyi Zhao, Yan Jin
Format: Article
Language:English
Published: BMC 2018-04-01
Series:Stem Cell Research & Therapy
Subjects:
Online Access:http://link.springer.com/article/10.1186/s13287-018-0821-5
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author Xinyu Qiu
Shiyu Liu
Hao Zhang
Bin Zhu
Yuting Su
Chenxi Zheng
Rong Tian
Miao Wang
Huijuan Kuang
Xinyi Zhao
Yan Jin
author_facet Xinyu Qiu
Shiyu Liu
Hao Zhang
Bin Zhu
Yuting Su
Chenxi Zheng
Rong Tian
Miao Wang
Huijuan Kuang
Xinyi Zhao
Yan Jin
author_sort Xinyu Qiu
collection DOAJ
description Abstract Background Skeletal muscle plays an important role in the body’s physiology but there are still no effective treatments for volumetric muscle loss (VML) resulting from severe traumatic injury or tumor excision. Recent studies show that a tissue engineering strategy using a compound containing mesenchymal stem cells (MSCs) and decellularized extracellular matrix (ECM) scaffold generates significant regenerative effects on VML injury, but the underlying mechanisms are not fully understood. Methods The characteristics of human umbilical cord MSCs, including multiplication capacity and multidifferentiation ability, were determined. We constructed a compound containing MSCs and decellularized ECM scaffold which was used for tissue regeneration in a VML model. Results We found that MSCs and decellularized ECM scaffold generated synergistic effects on promoting skeletal muscle tissue regeneration. Interestingly, both MSCs and decellularized ECM scaffold could promote macrophage polarization toward the M2 phenotype and suppress macrophage polarization toward the M1 phenotype, which is widely regarded as an important promoting factor in tissue regeneration. More importantly, MSCs and decellularized ECM scaffold generate synergistic promoting effects on macrophage polarization toward the M2 phenotype, not just an additive effect. Conclusions Our findings uncover a previously unknown mechanism that MSCs and decellularized ECM scaffold promote tissue regeneration via collaboratively regulating macrophage polarization.
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spelling doaj.art-f92ee3816cd443dda97f2b3db5a7df982022-12-22T01:56:44ZengBMCStem Cell Research & Therapy1757-65122018-04-019111510.1186/s13287-018-0821-5Mesenchymal stem cells and extracellular matrix scaffold promote muscle regeneration by synergistically regulating macrophage polarization toward the M2 phenotypeXinyu Qiu0Shiyu Liu1Hao Zhang2Bin Zhu3Yuting Su4Chenxi Zheng5Rong Tian6Miao Wang7Huijuan Kuang8Xinyi Zhao9Yan Jin10State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, Fourth Military Medical UniversityState Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, Fourth Military Medical UniversityState Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, Fourth Military Medical UniversityState Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, Fourth Military Medical UniversityState Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, Fourth Military Medical UniversityState Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, Fourth Military Medical UniversityState Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, Fourth Military Medical UniversityState Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, Fourth Military Medical UniversityState Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, Fourth Military Medical UniversityState Key Laboratory of Military Stomatology, Department of Dental Materials, Fourth Military Medical UniversityState Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, Fourth Military Medical UniversityAbstract Background Skeletal muscle plays an important role in the body’s physiology but there are still no effective treatments for volumetric muscle loss (VML) resulting from severe traumatic injury or tumor excision. Recent studies show that a tissue engineering strategy using a compound containing mesenchymal stem cells (MSCs) and decellularized extracellular matrix (ECM) scaffold generates significant regenerative effects on VML injury, but the underlying mechanisms are not fully understood. Methods The characteristics of human umbilical cord MSCs, including multiplication capacity and multidifferentiation ability, were determined. We constructed a compound containing MSCs and decellularized ECM scaffold which was used for tissue regeneration in a VML model. Results We found that MSCs and decellularized ECM scaffold generated synergistic effects on promoting skeletal muscle tissue regeneration. Interestingly, both MSCs and decellularized ECM scaffold could promote macrophage polarization toward the M2 phenotype and suppress macrophage polarization toward the M1 phenotype, which is widely regarded as an important promoting factor in tissue regeneration. More importantly, MSCs and decellularized ECM scaffold generate synergistic promoting effects on macrophage polarization toward the M2 phenotype, not just an additive effect. Conclusions Our findings uncover a previously unknown mechanism that MSCs and decellularized ECM scaffold promote tissue regeneration via collaboratively regulating macrophage polarization.http://link.springer.com/article/10.1186/s13287-018-0821-5Mesenchymal stem cellsMacrophage polarizationExtracellular matrixTissue regenerationVolumetric muscle loss
spellingShingle Xinyu Qiu
Shiyu Liu
Hao Zhang
Bin Zhu
Yuting Su
Chenxi Zheng
Rong Tian
Miao Wang
Huijuan Kuang
Xinyi Zhao
Yan Jin
Mesenchymal stem cells and extracellular matrix scaffold promote muscle regeneration by synergistically regulating macrophage polarization toward the M2 phenotype
Stem Cell Research & Therapy
Mesenchymal stem cells
Macrophage polarization
Extracellular matrix
Tissue regeneration
Volumetric muscle loss
title Mesenchymal stem cells and extracellular matrix scaffold promote muscle regeneration by synergistically regulating macrophage polarization toward the M2 phenotype
title_full Mesenchymal stem cells and extracellular matrix scaffold promote muscle regeneration by synergistically regulating macrophage polarization toward the M2 phenotype
title_fullStr Mesenchymal stem cells and extracellular matrix scaffold promote muscle regeneration by synergistically regulating macrophage polarization toward the M2 phenotype
title_full_unstemmed Mesenchymal stem cells and extracellular matrix scaffold promote muscle regeneration by synergistically regulating macrophage polarization toward the M2 phenotype
title_short Mesenchymal stem cells and extracellular matrix scaffold promote muscle regeneration by synergistically regulating macrophage polarization toward the M2 phenotype
title_sort mesenchymal stem cells and extracellular matrix scaffold promote muscle regeneration by synergistically regulating macrophage polarization toward the m2 phenotype
topic Mesenchymal stem cells
Macrophage polarization
Extracellular matrix
Tissue regeneration
Volumetric muscle loss
url http://link.springer.com/article/10.1186/s13287-018-0821-5
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