High paracrine activity of hADSCs cartilage microtissues inhibits extracellular matrix degradation and promotes cartilage regeneration

Due to its unique structure, articular cartilage has limited self-repair capacity. Microtissues are tiny tissue clusters that can mimic the function of target organs or tissues. Using cells alone for microtissue construction often results in the formation of necrotic cores. However, the extracellula...

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Main Authors: Wei Liu, Hongyu Jiang, Jiajie Chen, Yue Tian, Ying He, Ying Jiao, Yanjun Guan, Zhibo Jia, Yanbin Wu, Cheng Huang, Yiben Ouyang, Wenjing Xu, Jianhong Qi, Jiang Peng, Aiyuan Wang
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Language:English
Published: Elsevier 2025-02-01
Series:Materials Today Bio
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Online Access:http://www.sciencedirect.com/science/article/pii/S2590006424004332
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author Wei Liu
Hongyu Jiang
Jiajie Chen
Yue Tian
Ying He
Ying Jiao
Yanjun Guan
Zhibo Jia
Yanbin Wu
Cheng Huang
Yiben Ouyang
Wenjing Xu
Jianhong Qi
Jiang Peng
Aiyuan Wang
author_facet Wei Liu
Hongyu Jiang
Jiajie Chen
Yue Tian
Ying He
Ying Jiao
Yanjun Guan
Zhibo Jia
Yanbin Wu
Cheng Huang
Yiben Ouyang
Wenjing Xu
Jianhong Qi
Jiang Peng
Aiyuan Wang
author_sort Wei Liu
collection DOAJ
description Due to its unique structure, articular cartilage has limited self-repair capacity. Microtissues are tiny tissue clusters that can mimic the function of target organs or tissues. Using cells alone for microtissue construction often results in the formation of necrotic cores. However, the extracellular matrix (ECM) of native cartilage can provide structural support and is an ideal source of microcarriers. Autologous adipose-derived mesenchymal stem cells (ADSCs) and bone marrow mesenchymal stem cells (BMSCs) are widely used in cartilage tissue engineering. In this study, we fabricated microcarriers and compared the behavior of two homologous cell types in the microcarrier environment. The microcarrier environment highlighted the advantages of ADSCs and promoted the proliferation and migration of these cells. Then, ADSCs microtissues (ADSCs-MT) and BMSCs microtissues (BMSCs-MT) were fabricated using a three-dimensional dynamic culture system. In vitro and in vivo experiments verified that the cartilage regeneration ability of ADSCs-MT was significantly superior to that of BMSCs-MT. Transcriptomics revealed that ADSCs-MT showed significantly lower expression levels of ECM degradation, osteogenesis, and fibrocartilage markers. Finally, the protective effect of microtissues on inflammatory chondrocytes was validated. Overall, the ADSCs-MT constructed in this study achieved excellent cartilage regeneration and could be promising for the autologous application of cartilage microtissues.
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spelling doaj-art-863b4393cc3b47388f5e36a95857396b2025-01-17T04:52:00ZengElsevierMaterials Today Bio2590-00642025-02-0130101372High paracrine activity of hADSCs cartilage microtissues inhibits extracellular matrix degradation and promotes cartilage regenerationWei Liu0Hongyu Jiang1Jiajie Chen2Yue Tian3Ying He4Ying Jiao5Yanjun Guan6Zhibo Jia7Yanbin Wu8Cheng Huang9Yiben Ouyang10Wenjing Xu11Jianhong Qi12Jiang Peng13Aiyuan Wang14Institute of Orthopedics, The Fourth Medical Center of Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma & War Injuries PLA, No. 51 Fucheng Road, Beijing, 100048, PR China; College of Sports Medicine and Rehabilitation, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian, Shandong, 271016, PR ChinaInstitute of Orthopedics, The Fourth Medical Center of Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma & War Injuries PLA, No. 51 Fucheng Road, Beijing, 100048, PR China; Department of Orthopedic, The Affiliated Hospital, Southwest Medical University, Luzhou, PR ChinaInstitute of Orthopedics, The Fourth Medical Center of Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma & War Injuries PLA, No. 51 Fucheng Road, Beijing, 100048, PR China; School of Medicine, Nankai University, Tianjin, 300071, PR ChinaThe Second Medical Center of Chinese PLA General Hospital, PR ChinaInstitute of Orthopedics, The Fourth Medical Center of Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma & War Injuries PLA, No. 51 Fucheng Road, Beijing, 100048, PR ChinaCollege of Sports Medicine and Rehabilitation, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian, Shandong, 271016, PR ChinaInstitute of Orthopedics, The Fourth Medical Center of Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma & War Injuries PLA, No. 51 Fucheng Road, Beijing, 100048, PR ChinaInstitute of Orthopedics, The Fourth Medical Center of Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma & War Injuries PLA, No. 51 Fucheng Road, Beijing, 100048, PR ChinaInstitute of Orthopedics, The Fourth Medical Center of Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma & War Injuries PLA, No. 51 Fucheng Road, Beijing, 100048, PR ChinaInstitute of Orthopedics, The Fourth Medical Center of Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma & War Injuries PLA, No. 51 Fucheng Road, Beijing, 100048, PR China; Department of Orthopedic, The Affiliated Hospital, Southwest Medical University, Luzhou, PR ChinaInstitute of Orthopedics, The Fourth Medical Center of Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma & War Injuries PLA, No. 51 Fucheng Road, Beijing, 100048, PR China; School of Medicine, Nankai University, Tianjin, 300071, PR ChinaInstitute of Orthopedics, The Fourth Medical Center of Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma & War Injuries PLA, No. 51 Fucheng Road, Beijing, 100048, PR ChinaCollege of Sports Medicine and Rehabilitation, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian, Shandong, 271016, PR China; Corresponding author. College of Sports Medicine and Rehabilitation, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian, Shandong, 271016, PR China.Institute of Orthopedics, The Fourth Medical Center of Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma & War Injuries PLA, No. 51 Fucheng Road, Beijing, 100048, PR China; School of Medicine, Nankai University, Tianjin, 300071, PR China; Corresponding author. Institute of Orthopedics, The Fourth Medical Center of Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma & War Injuries PLA, No. 51 Fucheng Road, Beijing, 100048, PR China.Institute of Orthopedics, The Fourth Medical Center of Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma & War Injuries PLA, No. 51 Fucheng Road, Beijing, 100048, PR China; School of Medicine, Nankai University, Tianjin, 300071, PR China; Corresponding author. Institute of Orthopedics, The Fourth Medical Center of Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma & War Injuries PLA, No. 51 Fucheng Road, Beijing, 100048, PR China.Due to its unique structure, articular cartilage has limited self-repair capacity. Microtissues are tiny tissue clusters that can mimic the function of target organs or tissues. Using cells alone for microtissue construction often results in the formation of necrotic cores. However, the extracellular matrix (ECM) of native cartilage can provide structural support and is an ideal source of microcarriers. Autologous adipose-derived mesenchymal stem cells (ADSCs) and bone marrow mesenchymal stem cells (BMSCs) are widely used in cartilage tissue engineering. In this study, we fabricated microcarriers and compared the behavior of two homologous cell types in the microcarrier environment. The microcarrier environment highlighted the advantages of ADSCs and promoted the proliferation and migration of these cells. Then, ADSCs microtissues (ADSCs-MT) and BMSCs microtissues (BMSCs-MT) were fabricated using a three-dimensional dynamic culture system. In vitro and in vivo experiments verified that the cartilage regeneration ability of ADSCs-MT was significantly superior to that of BMSCs-MT. Transcriptomics revealed that ADSCs-MT showed significantly lower expression levels of ECM degradation, osteogenesis, and fibrocartilage markers. Finally, the protective effect of microtissues on inflammatory chondrocytes was validated. Overall, the ADSCs-MT constructed in this study achieved excellent cartilage regeneration and could be promising for the autologous application of cartilage microtissues.http://www.sciencedirect.com/science/article/pii/S2590006424004332Cartilage regenerationMicrotissuesMesenchymal stem cellsParacrine secretionECM degradation
spellingShingle Wei Liu
Hongyu Jiang
Jiajie Chen
Yue Tian
Ying He
Ying Jiao
Yanjun Guan
Zhibo Jia
Yanbin Wu
Cheng Huang
Yiben Ouyang
Wenjing Xu
Jianhong Qi
Jiang Peng
Aiyuan Wang
High paracrine activity of hADSCs cartilage microtissues inhibits extracellular matrix degradation and promotes cartilage regeneration
Materials Today Bio
Cartilage regeneration
Microtissues
Mesenchymal stem cells
Paracrine secretion
ECM degradation
title High paracrine activity of hADSCs cartilage microtissues inhibits extracellular matrix degradation and promotes cartilage regeneration
title_full High paracrine activity of hADSCs cartilage microtissues inhibits extracellular matrix degradation and promotes cartilage regeneration
title_fullStr High paracrine activity of hADSCs cartilage microtissues inhibits extracellular matrix degradation and promotes cartilage regeneration
title_full_unstemmed High paracrine activity of hADSCs cartilage microtissues inhibits extracellular matrix degradation and promotes cartilage regeneration
title_short High paracrine activity of hADSCs cartilage microtissues inhibits extracellular matrix degradation and promotes cartilage regeneration
title_sort high paracrine activity of hadscs cartilage microtissues inhibits extracellular matrix degradation and promotes cartilage regeneration
topic Cartilage regeneration
Microtissues
Mesenchymal stem cells
Paracrine secretion
ECM degradation
url http://www.sciencedirect.com/science/article/pii/S2590006424004332
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