Milena Deptuła1, Przemysław Karpowicz2, Anna Wardowska1,3, Piotr Sass4, Paweł Sosnowski4, Alina Mieczkowska5, Natalia Filipowicz5, Maria Dzierżyńska2, Justyna Sawicka2, Ewa Nowicka6, Paulina Langa3, Adriana Schumacher7, Mirosława Cichorek7, Jacek Zieliński8, Karolina Kondej9, Franciszek Kasprzykowski2, Artur Czupryn10, Łukasz Janus11, Piotr Mucha12, Piotr Skowron13, Arkadiusz Piotrowski5, Paweł Sachadyn4, Sylwia Rodziewicz-Motowidło2, Michał Pikuła1,3. 1. Laboratory of Tissue Engineering and Regenerative Medicine, Department of Embryology, Medical University of Gdansk, Gdansk, Poland. 2. Department of Biomedical Chemistry, Faculty of Chemistry, University of Gdansk, Gdansk, Poland. 3. Department of Clinical Immunology and Transplantology, Medical University of Gdansk, Gdansk, Poland. 4. Laboratory for Regenerative Biotechnology, Gdansk University of Technology, Gdansk, Poland. 5. Faculty of Pharmacy, Medical University of Gdansk, Gdansk, Poland. 6. Department of Clinical Anatomy, Medical University of Gdansk, Gdansk, Poland. 7. Department of Embryology, Medical University of Gdansk, Gdansk, Poland. 8. Department of Surgical Oncology, and Medical University of Gdansk, Gdansk, Poland. 9. Department of Plastic Surgery, Medical University of Gdansk, Gdansk, Poland. 10. Laboratory of Neurobiology, Nencki Institute of Experimental Biology PAS, Warsaw, Poland. 11. MedVentures company sp. z o.o., Gdansk, Poland. 12. Department of Biochemistry, and Faculty of Chemistry, University of Gdansk, Gdansk, Poland. 13. Department of Molecular Biotechnology, Faculty of Chemistry, University of Gdansk, Gdansk, Poland.
Abstract
Objective: This study evaluated the use of novel peptides derived from platelet-derived growth factor (PDGF-BB) as potential wound healing stimulants. One of the compounds (named PDGF2) was subjected for further research after cytotoxicity and proliferation assays on human skin cells. Further investigation included evaluation of: migration and chemotaxis of skin cells, immunological and allergic safety, the transcriptional analyses of adipose-derived stem cells (ASCs) and dermal fibroblasts stimulated with PDGF2, and the use of dorsal skin wound injury model to evaluate the effect of wound healing in mice. Approach: Colorimetric lactate dehydrogenase and tetrazolium assays were used to evaluate the cytotoxicity and the effect on proliferation. PDGF2 effect on migration and chemotaxis was also checked. Immunological safety and allergic potential were evaluated with a lymphocyte activation and basophil activation test. Transcriptional profiles of ASCs and primary fibroblasts were assessed after stimulation with PDGF2. Eight-week-old BALB/c female mice were used for dorsal skin wound injury model. Results: PDGF2 showed low cytotoxicity, pro-proliferative effects on human skin cells, high immunological safety, and accelerated wound healing in mouse model. Furthermore, transcriptomic analysis of ASCs and fibroblasts revealed the activation of processes involved in wound healing and indicated its safety. Innovation: A novel peptide derived from PDGF-BB was proved to be safe drug candidate in wound healing. We also present a multifaceted in vitro model for the initial screening of new compounds that may be potentially useful in wound healing stimulation. Conclusion: The results show that peptide derived from PDGF-BB is a promising drug candidate for wound treatment.
Objective: This study evaluated the use of novel peptides derived from platelet-derived growth factor (PDGF-BB) as potential wound healing stimulants. One of the compounds (named PDGF2) was subjected for further research after cytotoxicity and proliferation assays on human skin cells. Further investigation included evaluation of: migration and chemotaxis of skin cells, immunological and allergic safety, the transcriptional analyses of adipose-derived stem cells (ASCs) and dermal fibroblasts stimulated with PDGF2, and the use of dorsal skin wound injury model to evaluate the effect of wound healing in mice. Approach: Colorimetric lactate dehydrogenase and tetrazolium assays were used to evaluate the cytotoxicity and the effect on proliferation. PDGF2 effect on migration and chemotaxis was also checked. Immunological safety and allergic potential were evaluated with a lymphocyte activation and basophil activation test. Transcriptional profiles of ASCs and primary fibroblasts were assessed after stimulation with PDGF2. Eight-week-old BALB/c female mice were used for dorsal skin wound injury model. Results:PDGF2 showed low cytotoxicity, pro-proliferative effects on human skin cells, high immunological safety, and accelerated wound healing in mouse model. Furthermore, transcriptomic analysis of ASCs and fibroblasts revealed the activation of processes involved in wound healing and indicated its safety. Innovation: A novel peptide derived from PDGF-BB was proved to be safe drug candidate in wound healing. We also present a multifaceted in vitro model for the initial screening of new compounds that may be potentially useful in wound healing stimulation. Conclusion: The results show that peptide derived from PDGF-BB is a promising drug candidate for wound treatment.
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