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The aim of this study was to evaluate and compare the application of L-Mesitran Soft\u00ae, a product containing 40% medical grade honey (MGH), with other strategies to improve ovarian grafts\u2019 viability. For this purpose, bovine ovarian tissue was vitrified, warmed and randomly assigned to culture groups: (1) control, (2) MGH 0.2% in vitro, (3) MGH in vivo (direct application in the xenotransplantation), (4) vascular endothelial growth factor (VEGF 50 ng\/mL) and (5) vitamin D (100 Nm), during a 48 h period. A sixth group (6) of fragments was thawed on transplantation day and was not cultured. The tissue was xenotransplanted into immunodeficient (Rowett nude homozygous) ovariectomized rats. Grafts were analyzed 48 h after culture, and 7 and 28 days after transplantation. The tissue was subjected to histological and immunohistochemical analysis. Treatments using MGH showed the highest angiogenic and cell proliferation stimulation, with cellular apoptosis, within a healthy cellular turnover pathway. In conclusion, MGH should be considered as a potentially effective and less expensive strategy to improve ovarian tissue transplantation.<\/jats:p>","DOI":"10.3390\/bioengineering9080357","type":"journal-article","created":{"date-parts":[[2022,7,31]],"date-time":"2022-07-31T21:49:02Z","timestamp":1659304142000},"page":"357","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Medical Grade Honey as a Promising Treatment to Improve Ovarian Tissue Transplantation"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9829-1154","authenticated-orcid":false,"given":"Ana Rita","family":"Azevedo","sequence":"first","affiliation":[{"name":"INIAV\u2014Instituto Nacional de Investiga\u00e7\u00e3o Agr\u00e1ria e Veterin\u00e1ria I.P., Unidade de Biotecnologia e Recursos Gen\u00e9ticos, Quinta da Fonte Boa, 2005-048 Vale de Santar\u00e9m, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1977-5258","authenticated-orcid":false,"given":"Ana Sofia","family":"Pais","sequence":"additional","affiliation":[{"name":"Reproductive Medicine Unit, Centro Hospitalar e Universit\u00e1rio de Coimbra, 3000-075 Coimbra, Portugal"},{"name":"Faculty of Medicine, University of Coimbra, Azinhaga de Santa Comba, Celas, 3000-548 Coimbra, Portugal"},{"name":"Institute of Biophysics, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Centre of Investigation in Environment, Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Clinical Academic Center of Coimbra (CACC), 3004-561 Coimbra, Portugal"},{"name":"CNC\u2014Center for Neuroscience and Cell Biology, CIBB, University of Coimbra, Azinhaga de Santa Comba, Celas, 3004-504 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7423-2996","authenticated-orcid":false,"given":"Teresa","family":"Almeida-Santos","sequence":"additional","affiliation":[{"name":"Reproductive Medicine Unit, Centro Hospitalar e Universit\u00e1rio de Coimbra, 3000-075 Coimbra, Portugal"},{"name":"Faculty of Medicine, University of Coimbra, Azinhaga de Santa Comba, Celas, 3000-548 Coimbra, Portugal"},{"name":"CNC\u2014Center for Neuroscience and Cell Biology, CIBB, University of Coimbra, Azinhaga de Santa Comba, Celas, 3004-504 Coimbra, Portugal"}]},{"given":"Virg\u00ednia M. R.","family":"Pires","sequence":"additional","affiliation":[{"name":"CIISA\u2014Centre for Interdisciplinary Research in Animal Health, Faculdade de Medicina Veterin\u00e1ria, Universidade de Lisboa, 1300-477 Lisboa, Portugal"},{"name":"NZYTech\u2014Genes and Enzymes, Campos do Lumiar, Edif\u00edcio E, 1649-038 Lisboa, Portugal"}]},{"given":"Pedro","family":"Pessa","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Anatomia Patol\u00f3gica, Centro Hospitalar e Universit\u00e1rio de Coimbra, 3000-075 Coimbra, Portugal"}]},{"given":"Carla C.","family":"Marques","sequence":"additional","affiliation":[{"name":"INIAV\u2014Instituto Nacional de Investiga\u00e7\u00e3o Agr\u00e1ria e Veterin\u00e1ria I.P., Unidade de Biotecnologia e Recursos Gen\u00e9ticos, Quinta da Fonte Boa, 2005-048 Vale de Santar\u00e9m, Portugal"}]},{"given":"Sofia","family":"Nolasco","sequence":"additional","affiliation":[{"name":"CIISA\u2014Centre for Interdisciplinary Research in Animal Health, Faculdade de Medicina Veterin\u00e1ria, Universidade de Lisboa, 1300-477 Lisboa, Portugal"},{"name":"ESTeSl\u2014Escola Superior de Tecnologia da Sa\u00fade de Lisboa, Instituto Polit\u00e9cnico de Lisboa, 1990-096 Lisboa, Portugal"}]},{"given":"Pedro","family":"Castelo-Branco","sequence":"additional","affiliation":[{"name":"Faculdade de Medicina, Universidade do Algarve, 8005-139 Faro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1032-5987","authenticated-orcid":false,"given":"Jos\u00e9 A. M.","family":"Prates","sequence":"additional","affiliation":[{"name":"CIISA\u2014Centre for Interdisciplinary Research in Animal Health, Faculdade de Medicina Veterin\u00e1ria, Universidade de Lisboa, 1300-477 Lisboa, Portugal"},{"name":"Laborat\u00f3rio Associado para Ci\u00eancia Animal e Veterin\u00e1ria (AL4AnimalS), Faculdade de Medicina Veterin\u00e1ria, Universidade de Lisboa, 1300-477 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5165-3034","authenticated-orcid":false,"given":"Lu\u00eds","family":"Lopes-da-Costa","sequence":"additional","affiliation":[{"name":"CIISA\u2014Centre for Interdisciplinary Research in Animal Health, Faculdade de Medicina Veterin\u00e1ria, Universidade de Lisboa, 1300-477 Lisboa, Portugal"},{"name":"Laborat\u00f3rio Associado para Ci\u00eancia Animal e Veterin\u00e1ria (AL4AnimalS), Faculdade de Medicina Veterin\u00e1ria, Universidade de Lisboa, 1300-477 Lisboa, 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), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Centre of Investigation in Environment, Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Clinical Academic Center of Coimbra (CACC), 3004-561 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), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Centre of Investigation in Environment, Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Clinical Academic Center of Coimbra (CACC), 3004-561 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7514-6130","authenticated-orcid":false,"given":"Rosa M. L. N.","family":"Pereira","sequence":"additional","affiliation":[{"name":"INIAV\u2014Instituto Nacional de Investiga\u00e7\u00e3o Agr\u00e1ria e Veterin\u00e1ria I.P., Unidade de Biotecnologia e Recursos Gen\u00e9ticos, Quinta da Fonte Boa, 2005-048 Vale de Santar\u00e9m, Portugal"},{"name":"CIISA\u2014Centre for Interdisciplinary Research in Animal Health, Faculdade de Medicina Veterin\u00e1ria, Universidade de Lisboa, 1300-477 Lisboa, Portugal"}]},{"given":"Jorge M. B. G. 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