Enrichment of CD146 + Adipose-Derived Stem Cells in Combination with Articular Cartilage Extracellular Matrix Scaffold Promotes Cartilage Regeneration

Heterogeneity of mesenchymal stem cells (MSCs) influences the cell therapy outcome and the application in tissue engineering. Also, the application of subpopulations of MSCs in cartilage regeneration remains poorly characterized. CD146+ MSCs are identified as the natural ancestors of MSCs and the ex...

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Veröffentlicht in:Theranostics 2019-01, Vol.9 (17), p.5105-5121
Hauptverfasser: Li, Xu, Guo, Weimin, Zha, Kangkang, Jing, Xiaoguang, Wang, Mingjie, Zhang, Yu, Hao, Chunxiang, Gao, Shuang, Chen, Mingxue, Yuan, Zhiguo, Wang, Zhenyong, Zhang, Xueliang, Shen, Shi, Li, Haojiang, Zhang, Bin, Xian, Hai, Zhang, Yuan, Sui, Xiang, Qin, Ling, Peng, Jiang, Liu, Shuyun, Lu, Shibi, Guo, Quanyi
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container_end_page 5121
container_issue 17
container_start_page 5105
container_title Theranostics
container_volume 9
creator Li, Xu
Guo, Weimin
Zha, Kangkang
Jing, Xiaoguang
Wang, Mingjie
Zhang, Yu
Hao, Chunxiang
Gao, Shuang
Chen, Mingxue
Yuan, Zhiguo
Wang, Zhenyong
Zhang, Xueliang
Shen, Shi
Li, Haojiang
Zhang, Bin
Xian, Hai
Zhang, Yuan
Sui, Xiang
Qin, Ling
Peng, Jiang
Liu, Shuyun
Lu, Shibi
Guo, Quanyi
description Heterogeneity of mesenchymal stem cells (MSCs) influences the cell therapy outcome and the application in tissue engineering. Also, the application of subpopulations of MSCs in cartilage regeneration remains poorly characterized. CD146+ MSCs are identified as the natural ancestors of MSCs and the expression of CD146 are indicative of greater pluripotency and self-renewal potential. Here, we sorted a CD146 subpopulation from adipose-derived mesenchymal stem cells (ADSCs) for cartilage regeneration. : CD146 ADSCs were sorted using magnetic activated cell sorting (MACS). Cell surface markers, viability, apoptosis and proliferation were evaluated . The molecular signatures were analyzed by mRNA and protein expression profiling. By intra-articular injections of cells in a rat osteochondral defect model, we assessed the role of the specific subpopulation in cartilage microenvironment. Finally, CD146 ADSCs were combined with articular cartilage extracellular matrix (ACECM) scaffold for long term (3, 6 months) cartilage repair. : The enriched CD146 ADSCs showed a high expression of stem cell and pericyte markers, good viability, and immune characteristics to avoid allogeneic rejection. Gene and protein expression profiles revealed that the CD146 ADSCs had different cellular functions especially in regulation inflammation. In a rat model, CD146 ADSCs showed a better inflammation-modulating property in the early stage of intra-articular injections. Importantly, CD146 ADSCs exhibited good biocompatibility with the ACECM scaffold and the CD146 cell-scaffold composites produced less subcutaneous inflammation. The combination of CD146 ADSCs with ACECM scaffold can promote better cartilage regeneration in the long term. : Our data elucidated the function of the CD146 ADSC subpopulation, established their role in promoting cartilage repair, and highlighted the significance of cell subpopulations as a novel therapeutic for cartilage regeneration.
doi_str_mv 10.7150/thno.33904
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Also, the application of subpopulations of MSCs in cartilage regeneration remains poorly characterized. CD146+ MSCs are identified as the natural ancestors of MSCs and the expression of CD146 are indicative of greater pluripotency and self-renewal potential. Here, we sorted a CD146 subpopulation from adipose-derived mesenchymal stem cells (ADSCs) for cartilage regeneration. : CD146 ADSCs were sorted using magnetic activated cell sorting (MACS). Cell surface markers, viability, apoptosis and proliferation were evaluated . The molecular signatures were analyzed by mRNA and protein expression profiling. By intra-articular injections of cells in a rat osteochondral defect model, we assessed the role of the specific subpopulation in cartilage microenvironment. Finally, CD146 ADSCs were combined with articular cartilage extracellular matrix (ACECM) scaffold for long term (3, 6 months) cartilage repair. : The enriched CD146 ADSCs showed a high expression of stem cell and pericyte markers, good viability, and immune characteristics to avoid allogeneic rejection. Gene and protein expression profiles revealed that the CD146 ADSCs had different cellular functions especially in regulation inflammation. In a rat model, CD146 ADSCs showed a better inflammation-modulating property in the early stage of intra-articular injections. Importantly, CD146 ADSCs exhibited good biocompatibility with the ACECM scaffold and the CD146 cell-scaffold composites produced less subcutaneous inflammation. 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This work is published under https://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>The author(s) 2019</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c406t-778962802e65ad5c2019ce1a03f7e0c80cc7c407032c2bff98bb3987a1653d883</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6691381/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6691381/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31410204$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Li, Xu</creatorcontrib><creatorcontrib>Guo, Weimin</creatorcontrib><creatorcontrib>Zha, Kangkang</creatorcontrib><creatorcontrib>Jing, Xiaoguang</creatorcontrib><creatorcontrib>Wang, Mingjie</creatorcontrib><creatorcontrib>Zhang, Yu</creatorcontrib><creatorcontrib>Hao, Chunxiang</creatorcontrib><creatorcontrib>Gao, Shuang</creatorcontrib><creatorcontrib>Chen, Mingxue</creatorcontrib><creatorcontrib>Yuan, Zhiguo</creatorcontrib><creatorcontrib>Wang, Zhenyong</creatorcontrib><creatorcontrib>Zhang, Xueliang</creatorcontrib><creatorcontrib>Shen, Shi</creatorcontrib><creatorcontrib>Li, Haojiang</creatorcontrib><creatorcontrib>Zhang, Bin</creatorcontrib><creatorcontrib>Xian, Hai</creatorcontrib><creatorcontrib>Zhang, Yuan</creatorcontrib><creatorcontrib>Sui, Xiang</creatorcontrib><creatorcontrib>Qin, Ling</creatorcontrib><creatorcontrib>Peng, Jiang</creatorcontrib><creatorcontrib>Liu, Shuyun</creatorcontrib><creatorcontrib>Lu, Shibi</creatorcontrib><creatorcontrib>Guo, Quanyi</creatorcontrib><title>Enrichment of CD146 + Adipose-Derived Stem Cells in Combination with Articular Cartilage Extracellular Matrix Scaffold Promotes Cartilage Regeneration</title><title>Theranostics</title><addtitle>Theranostics</addtitle><description>Heterogeneity of mesenchymal stem cells (MSCs) influences the cell therapy outcome and the application in tissue engineering. 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Guo, Weimin ; Zha, Kangkang ; Jing, Xiaoguang ; Wang, Mingjie ; Zhang, Yu ; Hao, Chunxiang ; Gao, Shuang ; Chen, Mingxue ; Yuan, Zhiguo ; Wang, Zhenyong ; Zhang, Xueliang ; Shen, Shi ; Li, Haojiang ; Zhang, Bin ; Xian, Hai ; Zhang, Yuan ; Sui, Xiang ; Qin, Ling ; Peng, Jiang ; Liu, Shuyun ; Lu, Shibi ; Guo, Quanyi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c406t-778962802e65ad5c2019ce1a03f7e0c80cc7c407032c2bff98bb3987a1653d883</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Adipose Tissue - cytology</topic><topic>Animals</topic><topic>Antibodies</topic><topic>Apoptosis</topic><topic>Arthritis</topic><topic>Bone marrow</topic><topic>Cartilage</topic><topic>Cartilage, Articular - metabolism</topic><topic>Cartilage, Articular - physiology</topic><topic>CD146 Antigen - genetics</topic><topic>CD146 Antigen - metabolism</topic><topic>Cells, Cultured</topic><topic>Extracellular matrix</topic><topic>Extracellular Matrix - chemistry</topic><topic>Extracellular Matrix - metabolism</topic><topic>Humans</topic><topic>Mesenchymal Stem Cell Transplantation - methods</topic><topic>Mesenchymal Stem Cells - cytology</topic><topic>Mesenchymal Stem Cells - metabolism</topic><topic>Proteins</topic><topic>Rabbits</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Regeneration</topic><topic>Research Paper</topic><topic>Software</topic><topic>Stem cells</topic><topic>Tissue engineering</topic><topic>Tissue Engineering - methods</topic><topic>Tissue Scaffolds - chemistry</topic><topic>Umbilical cord</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Li, Xu</creatorcontrib><creatorcontrib>Guo, Weimin</creatorcontrib><creatorcontrib>Zha, Kangkang</creatorcontrib><creatorcontrib>Jing, Xiaoguang</creatorcontrib><creatorcontrib>Wang, Mingjie</creatorcontrib><creatorcontrib>Zhang, Yu</creatorcontrib><creatorcontrib>Hao, Chunxiang</creatorcontrib><creatorcontrib>Gao, Shuang</creatorcontrib><creatorcontrib>Chen, Mingxue</creatorcontrib><creatorcontrib>Yuan, Zhiguo</creatorcontrib><creatorcontrib>Wang, Zhenyong</creatorcontrib><creatorcontrib>Zhang, Xueliang</creatorcontrib><creatorcontrib>Shen, Shi</creatorcontrib><creatorcontrib>Li, Haojiang</creatorcontrib><creatorcontrib>Zhang, Bin</creatorcontrib><creatorcontrib>Xian, Hai</creatorcontrib><creatorcontrib>Zhang, Yuan</creatorcontrib><creatorcontrib>Sui, Xiang</creatorcontrib><creatorcontrib>Qin, Ling</creatorcontrib><creatorcontrib>Peng, Jiang</creatorcontrib><creatorcontrib>Liu, Shuyun</creatorcontrib><creatorcontrib>Lu, Shibi</creatorcontrib><creatorcontrib>Guo, Quanyi</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health &amp; 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Also, the application of subpopulations of MSCs in cartilage regeneration remains poorly characterized. CD146+ MSCs are identified as the natural ancestors of MSCs and the expression of CD146 are indicative of greater pluripotency and self-renewal potential. Here, we sorted a CD146 subpopulation from adipose-derived mesenchymal stem cells (ADSCs) for cartilage regeneration. : CD146 ADSCs were sorted using magnetic activated cell sorting (MACS). Cell surface markers, viability, apoptosis and proliferation were evaluated . The molecular signatures were analyzed by mRNA and protein expression profiling. By intra-articular injections of cells in a rat osteochondral defect model, we assessed the role of the specific subpopulation in cartilage microenvironment. Finally, CD146 ADSCs were combined with articular cartilage extracellular matrix (ACECM) scaffold for long term (3, 6 months) cartilage repair. : The enriched CD146 ADSCs showed a high expression of stem cell and pericyte markers, good viability, and immune characteristics to avoid allogeneic rejection. Gene and protein expression profiles revealed that the CD146 ADSCs had different cellular functions especially in regulation inflammation. In a rat model, CD146 ADSCs showed a better inflammation-modulating property in the early stage of intra-articular injections. Importantly, CD146 ADSCs exhibited good biocompatibility with the ACECM scaffold and the CD146 cell-scaffold composites produced less subcutaneous inflammation. The combination of CD146 ADSCs with ACECM scaffold can promote better cartilage regeneration in the long term. : Our data elucidated the function of the CD146 ADSC subpopulation, established their role in promoting cartilage repair, and highlighted the significance of cell subpopulations as a novel therapeutic for cartilage regeneration.</abstract><cop>Australia</cop><pub>Ivyspring International Publisher Pty Ltd</pub><pmid>31410204</pmid><doi>10.7150/thno.33904</doi><tpages>17</tpages><oa>free_for_read</oa></addata></record>
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subjects Adipose Tissue - cytology
Animals
Antibodies
Apoptosis
Arthritis
Bone marrow
Cartilage
Cartilage, Articular - metabolism
Cartilage, Articular - physiology
CD146 Antigen - genetics
CD146 Antigen - metabolism
Cells, Cultured
Extracellular matrix
Extracellular Matrix - chemistry
Extracellular Matrix - metabolism
Humans
Mesenchymal Stem Cell Transplantation - methods
Mesenchymal Stem Cells - cytology
Mesenchymal Stem Cells - metabolism
Proteins
Rabbits
Rats
Rats, Sprague-Dawley
Regeneration
Research Paper
Software
Stem cells
Tissue engineering
Tissue Engineering - methods
Tissue Scaffolds - chemistry
Umbilical cord
title Enrichment of CD146 + Adipose-Derived Stem Cells in Combination with Articular Cartilage Extracellular Matrix Scaffold Promotes Cartilage Regeneration
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