Publications Repository - Gdańsk University of Technology

Background:Most studies on regenerative medicine focus on cell-based therapies and transplantations.Small-molecule therapeutics, though proved effective in different medical conditions, have not been extensivelyinvestigated in regenerative research. It is known that healing potential decreases with development and devel-opmental changes are driven by epigenetic mechanisms, which suggests epigenetic repression of regenerativecapacity.Methods:We applied zebularine, a nucleoside inhibitor of DNA methyltransferases, to stimulate the regenerativeresponse in a model of ear pinna injury in mice.Findings:We observed the regeneration of complex tissue that was manifested as improved ear hole repair inmice that received intraperitoneal injections of zebularine. Six weeks after injury, the mean hole area decreasedby 83.2 ± 9.4% in zebularine-treated and by 43.6 ± 15.4% in control mice (pb10−30). Combined delivery ofzebularine and retinoic acid potentiated and accelerated this effect, resulting in complete ear hole closure withinthree weeks after injury. We found a decrease in DNA methylation and transcriptional activation ofneurodevelopmental and pluripotency genes in the regenerating tissues.Interpretation:This study is thefirst to demonstrate an effective induction of complex tissue regeneration in adultmammals using zebularine. We showed that the synergistic action of an epigenetic drug (zebularine) and a tran-scriptional activator (retinoic acid) could be effectively utilized to induce the regenerative response, thus delin-eating a novel pharmacological strategy for regeneration. The strategy was effective in the model of ear pinnaregeneration in mice, but zebularine acts on different cell types, therefore, a similar approach can be tested inother tissues and organs

Authors

• dr inż. Piotr Sass link open in new tab ,
• dr inż. Paweł Sosnowski link open in new tab ,
• dr inż. Justyna Podolak-Popinigis link open in new tab ,
• dr inż. Bartosz Górnikiewicz link open in new tab ,
• Jolanta Kamińska link open in new tab ,
• Milena Deptuła,
• Ewa Nowicka,
• Anna Wardowska,
• Jarosław Ruczyński link open in new tab ,
• Piotr Rekowski link open in new tab ,
• Piotr Rogujski,
• Natalia Filipowicz,
• Alina Mieczkowska,
• Grażyna Peszyńska-Sularz link open in new tab ,
• Łukasz Janusz link open in new tab ,
• prof. dr hab. Piotr Skowron,
• dr Artur Czupryn,
• dr hab. Piotr Mucha,
• dr hab. Arkadiusz Piotrowski,
• dr hab. Sylwia Rodziewicz-Motowidło,
• dr hab. med. Michał Pikuła,
• prof. dr hab. inż. Paweł Sachadyn link open in new tab