{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T21:59:36Z","timestamp":1775685576732,"version":"3.50.1"},"reference-count":99,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2024,1,31]],"date-time":"2024-01-31T00:00:00Z","timestamp":1706659200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Portuguese Foundation for Science and Technology (FCT)","award":["10.54499\/UIDB\/04539\/2020"],"award-info":[{"award-number":["10.54499\/UIDB\/04539\/2020"]}]},{"name":"The Portuguese Foundation for Science and Technology (FCT)","award":["10.54499\/UIDP\/04539\/2020"],"award-info":[{"award-number":["10.54499\/UIDP\/04539\/2020"]}]},{"name":"The Portuguese Foundation for Science and Technology (FCT)","award":["10.54499\/LA\/P\/0058\/2020"],"award-info":[{"award-number":["10.54499\/LA\/P\/0058\/2020"]}]},{"name":"The Portuguese Foundation for Science and Technology (FCT)","award":["CENTRO-01-0145-FEDER-028871"],"award-info":[{"award-number":["CENTRO-01-0145-FEDER-028871"]}]},{"name":"Associated Laboratory","award":["10.54499\/UIDB\/04539\/2020"],"award-info":[{"award-number":["10.54499\/UIDB\/04539\/2020"]}]},{"name":"Associated Laboratory","award":["10.54499\/UIDP\/04539\/2020"],"award-info":[{"award-number":["10.54499\/UIDP\/04539\/2020"]}]},{"name":"Associated Laboratory","award":["10.54499\/LA\/P\/0058\/2020"],"award-info":[{"award-number":["10.54499\/LA\/P\/0058\/2020"]}]},{"name":"Associated Laboratory","award":["CENTRO-01-0145-FEDER-028871"],"award-info":[{"award-number":["CENTRO-01-0145-FEDER-028871"]}]},{"name":"STEM@REST Project","award":["10.54499\/UIDB\/04539\/2020"],"award-info":[{"award-number":["10.54499\/UIDB\/04539\/2020"]}]},{"name":"STEM@REST Project","award":["10.54499\/UIDP\/04539\/2020"],"award-info":[{"award-number":["10.54499\/UIDP\/04539\/2020"]}]},{"name":"STEM@REST Project","award":["10.54499\/LA\/P\/0058\/2020"],"award-info":[{"award-number":["10.54499\/LA\/P\/0058\/2020"]}]},{"name":"STEM@REST Project","award":["CENTRO-01-0145-FEDER-028871"],"award-info":[{"award-number":["CENTRO-01-0145-FEDER-028871"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Reversine is a purine derivative that has been investigated with regard to its biological effects, such as its anticancer properties and, mostly, its ability to induce the dedifferentiation of adult cells, increasing their plasticity. The obtained dedifferentiated cells have a high potential for use in regenerative procedures, such as regenerative dentistry (RD). Instead of replacing the lost or damaged oral tissues with synthetic materials, RD uses stem cells combined with matrices and an appropriate microenvironment to achieve tissue regeneration. However, the currently available stem cell sources present limitations, thus restricting the potential of RD. Based on this problem, new sources of stem cells are fundamental. This work aims to characterize mouse gingival fibroblasts (GFs) after dedifferentiation with reversine. Different administration protocols were tested, and the cells obtained were evaluated regarding their cell metabolism, protein and DNA contents, cell cycle changes, morphology, cell death, genotoxicity, and acquisition of stem cell characteristics. Additionally, their teratoma potential was evaluated after in vivo transplantation. Reversine caused toxicity at higher concentrations, with decreased cell metabolic activity and protein content. The cells obtained displayed polyploidy, a cycle arrest in the G2\/M phase, and showed an enlarged size. Additionally, apoptosis and genotoxicity were found at higher reversine concentrations. A subpopulation of the GFs possessed stem properties, as supported by the increased expression of CD90, CD105, and TERT, the existence of a CD106+ population, and their trilineage differentiation capacity. The dedifferentiated cells did not induce teratoma formation. The extensive characterization performed shows that significant functional, morphological, and genetic changes occur during the dedifferentiation process. The dedifferentiated cells have some stem-like characteristics, which are of interest for RD.<\/jats:p>","DOI":"10.3390\/pharmaceutics16020207","type":"journal-article","created":{"date-parts":[[2024,1,31]],"date-time":"2024-01-31T08:44:06Z","timestamp":1706690646000},"page":"207","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["In Vitro Characterization of Reversine-Treated Gingival Fibroblasts and Their Safety Evaluation after In Vivo Transplantation"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9269-5417","authenticated-orcid":false,"given":"Carlos Miguel","family":"Marto","sequence":"first","affiliation":[{"name":"Institute of Experimental Pathology, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Institute of Biophysics, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Institute of Integrated Clinical Practice and Laboratory of Evidence-Based and Precision Dentistry, Faculty of Medicine, University of Coimbra, 3000-075 Coimbra, Portugal"},{"name":"Coimbra Institute for Clinical and Biomedical Research (iCBR), Area of Environment, Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Centre for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Clinical Academic Center of Coimbra (CACC), 3004-561 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0689-6007","authenticated-orcid":false,"given":"Mafalda","family":"Laranjo","sequence":"additional","affiliation":[{"name":"Institute of Biophysics, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Coimbra Institute for Clinical and Biomedical Research (iCBR), Area of Environment, Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Centre for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Clinical Academic Center of Coimbra (CACC), 3004-561 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1470-4802","authenticated-orcid":false,"given":"Ana Cristina","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Coimbra Institute for Clinical and Biomedical Research (iCBR), Area of Environment, Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Centre for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Clinical Academic Center of Coimbra (CACC), 3004-561 Coimbra, Portugal"},{"name":"Laboratory of Oncobiology and Hematology (LOH) and University Clinic of Hematology, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6154-4173","authenticated-orcid":false,"given":"Anabela","family":"Paula","sequence":"additional","affiliation":[{"name":"Institute of Integrated Clinical Practice and Laboratory of Evidence-Based and Precision Dentistry, Faculty of Medicine, University of Coimbra, 3000-075 Coimbra, Portugal"},{"name":"Coimbra Institute for Clinical and Biomedical Research (iCBR), Area of Environment, Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Centre for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Clinical Academic Center of Coimbra (CACC), 3004-561 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0755-8077","authenticated-orcid":false,"given":"Joana","family":"Jorge","sequence":"additional","affiliation":[{"name":"Coimbra Institute for Clinical and Biomedical Research (iCBR), Area of Environment, Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Centre for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Clinical Academic Center of Coimbra (CACC), 3004-561 Coimbra, Portugal"},{"name":"Laboratory of Oncobiology and Hematology (LOH) and University Clinic of Hematology, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7202-8059","authenticated-orcid":false,"given":"Rui","family":"Caetano-Oliveira","sequence":"additional","affiliation":[{"name":"Coimbra Institute for Clinical and Biomedical Research (iCBR), Area of Environment, Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Pathology Department, Centro Hospitalar e Universit\u00e1rio de Coimbra, 3000-075 Coimbra, Portugal"},{"name":"Germano de Sousa\u2014Centro de Diagn\u00f3stico Histopatol\u00f3gico CEDAP, University of Coimbra, 3000-377 Coimbra, Portugal"}]},{"given":"Maria In\u00eas","family":"Sousa","sequence":"additional","affiliation":[{"name":"Centre for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Department of Life Sciences, University of Coimbra, 3000-456 Coimbra, Portugal"},{"name":"CNC\u2014Center for Neuroscience and Cell Biology, University of Coimbra, 3000-548 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7836-8161","authenticated-orcid":false,"given":"B\u00e1rbara","family":"Oliveiros","sequence":"additional","affiliation":[{"name":"Coimbra Institute for Clinical and Biomedical Research (iCBR), Area of Environment, Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Centre for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Clinical Academic Center of Coimbra (CACC), 3004-561 Coimbra, Portugal"},{"name":"Laboratory of Biostatistics and Medical Informatics, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1172-4018","authenticated-orcid":false,"given":"Jo\u00e3o","family":"Ramalho-Santos","sequence":"additional","affiliation":[{"name":"Centre for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Department of Life Sciences, University of Coimbra, 3000-456 Coimbra, Portugal"},{"name":"CNC\u2014Center for Neuroscience and Cell Biology, University of Coimbra, 3000-548 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4142-4841","authenticated-orcid":false,"given":"Ana Bela","family":"Sarmento-Ribeiro","sequence":"additional","affiliation":[{"name":"Coimbra Institute for Clinical and Biomedical Research (iCBR), Area of Environment, Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Centre for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Clinical Academic Center of Coimbra (CACC), 3004-561 Coimbra, Portugal"},{"name":"Laboratory of Oncobiology and Hematology (LOH) and University Clinic of Hematology, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5968-6161","authenticated-orcid":false,"given":"Manuel","family":"Marques-Ferreira","sequence":"additional","affiliation":[{"name":"Coimbra Institute for Clinical and Biomedical Research (iCBR), Area of Environment, Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Centre for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Clinical Academic Center of Coimbra (CACC), 3004-561 Coimbra, Portugal"},{"name":"Institute of Endodontics, Faculty of Medicine, University of Coimbra, 3000-075 Coimbra, Portugal"}]},{"given":"Ant\u00f3nio","family":"Cabrita","sequence":"additional","affiliation":[{"name":"Institute of Experimental Pathology, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7202-1650","authenticated-orcid":false,"given":"Maria Filomena","family":"Botelho","sequence":"additional","affiliation":[{"name":"Institute of Biophysics, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Coimbra Institute for Clinical and Biomedical Research (iCBR), Area of Environment, Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Centre for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Clinical Academic Center of Coimbra (CACC), 3004-561 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5759-5557","authenticated-orcid":false,"given":"Eunice","family":"Carrilho","sequence":"additional","affiliation":[{"name":"Institute of Integrated Clinical Practice and Laboratory of Evidence-Based and Precision Dentistry, Faculty of Medicine, University of Coimbra, 3000-075 Coimbra, Portugal"},{"name":"Coimbra Institute for Clinical and Biomedical Research (iCBR), Area of Environment, Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Centre for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Clinical Academic Center of Coimbra (CACC), 3004-561 Coimbra, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,31]]},"reference":[{"key":"ref_1","first-page":"S25","article-title":"Reversine Increases Multipotent Human Mesenchymal Cells Differentiation 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