{"title":"Periodontal ligament stem cell tissue engineering scaffolds can guide and promote canine periodontal tissue regeneration.","authors":"Pengxiu Dai, Guixiang Qi, Mingde Zhu, Qingjie Du, Keyi Wang, Yaxin Gao, Mengnan Li, Xiancheng Feng, Xinke Zhang","doi":"10.3389/fvets.2024.1465879","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The immunogenicity of allogeneic mesenchymal stem cells (MSCs) is significantly enhanced after transplantation or differentiation, and these cells can be recognized and cleared by recipient immune cells. Graft rejection has become a major obstacle to improving the therapeutic effect of allogeneic MSCs or, after their differentiation, transplantation in the treatment of diabetes and other diseases. Solving this problem is helpful for prolonging the time that cells play a role in the recipient body and for significantly improving the clinical therapeutic effect.</p><p><strong>Methods: </strong>In this study, canine adipose-derived mesenchymal stem cells (ADSCs) were used as seed cells, and gene editing technology was used to knock out the B2M gene in these cells and cooperate with the overexpression of the PD-L1 gene. Gene-edited ADSCs (GeADSCs), whose biological characteristics and safety are not different from those of normal canine ADSCs, have been obtained.</p><p><strong>Results: </strong>The immunogenicity of GeADSCs is reduced, the immune escape ability of GeADSCs is enhanced, and GeADSCs can remain in the body for a longer time. Using the optimized induction program, the efficiency of the differentiation of GeADSCs into new islet β-cells was increased, and the maturity of the new islet β-cells was increased. The immunogenicity of new islet β-cells decreased, and their immune escape ability was enhanced after the cells were transplanted into diabetic dogs (the graft site was prevascularized by the implantation of a scaffold to form a vascularized pouch). The number of infiltrating immune cells and the content of immune factors were decreased at the graft site.</p><p><strong>Conclusions: </strong>New islet β-cell transplantation, which has low immunogenicity, can reverse diabetes in dogs, and the therapeutic effect of cell transplantation is significantly enhanced. This study provides a new method for prolonging the survival and functional time of cells in transplant recipients and significantly improving the clinical therapeutic effect.</p>","PeriodicalId":12772,"journal":{"name":"Frontiers in Veterinary Science","volume":null,"pages":null},"PeriodicalIF":2.6000,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11496256/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Veterinary Science","FirstCategoryId":"97","ListUrlMain":"https://doi.org/10.3389/fvets.2024.1465879","RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"VETERINARY SCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
Background: The immunogenicity of allogeneic mesenchymal stem cells (MSCs) is significantly enhanced after transplantation or differentiation, and these cells can be recognized and cleared by recipient immune cells. Graft rejection has become a major obstacle to improving the therapeutic effect of allogeneic MSCs or, after their differentiation, transplantation in the treatment of diabetes and other diseases. Solving this problem is helpful for prolonging the time that cells play a role in the recipient body and for significantly improving the clinical therapeutic effect.
Methods: In this study, canine adipose-derived mesenchymal stem cells (ADSCs) were used as seed cells, and gene editing technology was used to knock out the B2M gene in these cells and cooperate with the overexpression of the PD-L1 gene. Gene-edited ADSCs (GeADSCs), whose biological characteristics and safety are not different from those of normal canine ADSCs, have been obtained.
Results: The immunogenicity of GeADSCs is reduced, the immune escape ability of GeADSCs is enhanced, and GeADSCs can remain in the body for a longer time. Using the optimized induction program, the efficiency of the differentiation of GeADSCs into new islet β-cells was increased, and the maturity of the new islet β-cells was increased. The immunogenicity of new islet β-cells decreased, and their immune escape ability was enhanced after the cells were transplanted into diabetic dogs (the graft site was prevascularized by the implantation of a scaffold to form a vascularized pouch). The number of infiltrating immune cells and the content of immune factors were decreased at the graft site.
Conclusions: New islet β-cell transplantation, which has low immunogenicity, can reverse diabetes in dogs, and the therapeutic effect of cell transplantation is significantly enhanced. This study provides a new method for prolonging the survival and functional time of cells in transplant recipients and significantly improving the clinical therapeutic effect.
期刊介绍：
Frontiers in Veterinary Science is a global, peer-reviewed, Open Access journal that bridges animal and human health, brings a comparative approach to medical and surgical challenges, and advances innovative biotechnology and therapy.
Veterinary research today is interdisciplinary, collaborative, and socially relevant, transforming how we understand and investigate animal health and disease. Fundamental research in emerging infectious diseases, predictive genomics, stem cell therapy, and translational modelling is grounded within the integrative social context of public and environmental health, wildlife conservation, novel biomarkers, societal well-being, and cutting-edge clinical practice and specialization. Frontiers in Veterinary Science brings a 21st-century approach—networked, collaborative, and Open Access—to communicate this progress and innovation to both the specialist and to the wider audience of readers in the field.
Frontiers in Veterinary Science publishes articles on outstanding discoveries across a wide spectrum of translational, foundational, and clinical research. The journal''s mission is to bring all relevant veterinary sciences together on a single platform with the goal of improving animal and human health.
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