Development of a Peptide Derived from Platelet-Derived Growth Factor (PDGF-BB) into a Potential Drug Candidate for the Treatment of Wounds
Autor: | Piotr Sass, Łukasz Janus, Piotr Mucha, Alina Mieczkowska, Adriana Schumacher, Maria Dzierżyńska, Arkadiusz Piotrowski, Paweł Sachadyn, Jacek Zieliński, Anna Wardowska, Artur Czupryn, Franciszek Kasprzykowski, Sylwia Rodziewicz-Motowidło, Mirosława Cichorek, Piotr M. Skowron, Justyna Sawicka, Ewa Nowicka, Paweł Sosnowski, Paulina Langa, Natalia Filipowicz, Przemysław Karpowicz, Michał Pikuła, Karolina Kondej, Milena Deptuła |
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Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Platelet-derived growth factor medicine.medical_treatment Becaplermin Human skin Pharmacology Critical Care and Intensive Care Medicine Technology Advances Mice 030207 dermatology & venereal diseases 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Animals Humans Medicine Cytotoxicity Skin Mice Inbred BALB C Wound Healing integumentary system biology business.industry Chemotaxis Stem Cells Growth factor Fibroblasts Recombinant Proteins 030104 developmental biology Adipose Tissue Pharmaceutical Preparations chemistry Emergency Medicine biology.protein Female Stem cell business Wound healing Platelet-derived growth factor receptor |
Zdroj: | Adv Wound Care (New Rochelle) |
ISSN: | 2162-1934 2162-1918 |
Popis: | 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. |
Databáze: | OpenAIRE |
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