{"title":"Mesenchymal stem cell-derived protein extract induces periodontal regeneration","authors":"Yihao Peng , Kengo Iwasaki , Yoichiro Taguchi , Isao Ishikawa , Makoto Umeda","doi":"10.1016/j.jcyt.2024.10.003","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Periodontal disease is characterized by chronic inflammation and destruction of supporting periodontal tissues, ultimately leading to tooth loss. In recent years, “cell-free treatment” without stem cell transplantation has attracted considerable attention for tissue regeneration. This study investigated the effects of extracts of mesenchymal stem cells (MSC-extract) and their protein components (MSC-protein) on the proliferation and migration of periodontal ligament (PDL) cells and whether MSC-protein can induce periodontal regeneration.</div></div><div><h3>Methods</h3><div>MSC-extract and MSC-protein were obtained by subjecting mesenchymal stem cells (MSCs) to freeze–thaw cycles and acetone precipitation. Cell proliferation was examined using a WST-8 assay and Ki67 immunostaining, and cell migration was examined using Boyden chambers. The MSC-protein content was analyzed using liquid chromatography-mass spectrometry, protein arrays, and enzyme-linked immunosorbent assays (ELISAs). Gene expression in MSC-protein-treated PDL cells was examined using RNA-sequencing and Gene Ontology analyses. The regenerative potential of MSC-protein was examined using micro-computer tomography (CT) and histological analyses after transplantation into a rat periodontal defect model.</div></div><div><h3>Results</h3><div>MSC-extract and MSC-protein promoted the proliferation and migration of PDL cells. Protein array and ELISA revealed that MSC-protein contained high concentrations of basic fibroblast growth factor (bFGF) and hepatocyte growth factor (HGF). Exogenous bFGF promoted the proliferation and migration of PDL cells. Furthermore, the transplantation of MSC-protein enhanced periodontal tissue regeneration with the formation of new alveolar bone and PDLs.</div></div><div><h3>Conclusions</h3><div>These results indicate that the MSC-protein promotes the proliferation and migration of PDL cells and induces significant periodontal tissue regeneration, suggesting that the MSC-protein could be used as a new cell-free treatment for periodontal disease.</div></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"27 2","pages":"Pages 201-212"},"PeriodicalIF":3.7000,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cytotherapy","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1465324924008922","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background
Periodontal disease is characterized by chronic inflammation and destruction of supporting periodontal tissues, ultimately leading to tooth loss. In recent years, “cell-free treatment” without stem cell transplantation has attracted considerable attention for tissue regeneration. This study investigated the effects of extracts of mesenchymal stem cells (MSC-extract) and their protein components (MSC-protein) on the proliferation and migration of periodontal ligament (PDL) cells and whether MSC-protein can induce periodontal regeneration.
Methods
MSC-extract and MSC-protein were obtained by subjecting mesenchymal stem cells (MSCs) to freeze–thaw cycles and acetone precipitation. Cell proliferation was examined using a WST-8 assay and Ki67 immunostaining, and cell migration was examined using Boyden chambers. The MSC-protein content was analyzed using liquid chromatography-mass spectrometry, protein arrays, and enzyme-linked immunosorbent assays (ELISAs). Gene expression in MSC-protein-treated PDL cells was examined using RNA-sequencing and Gene Ontology analyses. The regenerative potential of MSC-protein was examined using micro-computer tomography (CT) and histological analyses after transplantation into a rat periodontal defect model.
Results
MSC-extract and MSC-protein promoted the proliferation and migration of PDL cells. Protein array and ELISA revealed that MSC-protein contained high concentrations of basic fibroblast growth factor (bFGF) and hepatocyte growth factor (HGF). Exogenous bFGF promoted the proliferation and migration of PDL cells. Furthermore, the transplantation of MSC-protein enhanced periodontal tissue regeneration with the formation of new alveolar bone and PDLs.
Conclusions
These results indicate that the MSC-protein promotes the proliferation and migration of PDL cells and induces significant periodontal tissue regeneration, suggesting that the MSC-protein could be used as a new cell-free treatment for periodontal disease.
期刊介绍:
The journal brings readers the latest developments in the fast moving field of cellular therapy in man. This includes cell therapy for cancer, immune disorders, inherited diseases, tissue repair and regenerative medicine. The journal covers the science, translational development and treatment with variety of cell types including hematopoietic stem cells, immune cells (dendritic cells, NK, cells, T cells, antigen presenting cells) mesenchymal stromal cells, adipose cells, nerve, muscle, vascular and endothelial cells, and induced pluripotential stem cells. We also welcome manuscripts on subcellular derivatives such as exosomes. A specific focus is on translational research that brings cell therapy to the clinic. Cytotherapy publishes original papers, reviews, position papers editorials, commentaries and letters to the editor. We welcome "Protocols in Cytotherapy" bringing standard operating procedure for production specific cell types for clinical use within the reach of the readership.