Laboratory of Tissue Engineering and Regenerative Medicine, Department of Embryology, Medical University of Gdansk, Gdansk, Poland.
Department of Biomedical Chemistry, Faculty of Chemistry, University of Gdansk, Gdansk, Poland.
Adv Wound Care (New Rochelle). 2020 Dec;9(12):657-675. doi: 10.1089/wound.2019.1051. Epub 2019 Oct 29.
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. 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. 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. A novel peptide derived from PDGF-BB was proved to be safe drug candidate in wound healing. We also present a multifaceted model for the initial screening of new compounds that may be potentially useful in wound healing stimulation. The results show that peptide derived from PDGF-BB is a promising drug candidate for wound treatment.
本研究评估了源自血小板衍生生长因子(PDGF-BB)的新型肽作为潜在的伤口愈合刺激剂的用途。在对人皮肤细胞进行细胞毒性和增殖测定后,对一种化合物(命名为 PDGF2)进行了进一步研究。进一步的研究包括:皮肤细胞的迁移和趋化性、免疫和过敏安全性、用 PDGF2 刺激脂肪来源干细胞(ASCs)和真皮成纤维细胞的转录分析,以及使用背部皮肤伤口损伤模型评估在小鼠中伤口愈合的效果。使用比色乳酸脱氢酶和四唑盐测定法来评估细胞毒性和对增殖的影响。还检查了 PDGF2 对迁移和趋化性的作用。通过淋巴细胞激活和嗜碱性粒细胞激活测试评估免疫安全性和过敏潜力。用 PDGF2 刺激后评估 ASCs 和原代成纤维细胞的转录谱。使用 8 周龄 BALB/c 雌性小鼠进行背部皮肤伤口损伤模型。PDGF2 表现出低细胞毒性、对人皮肤细胞的促增殖作用、高免疫安全性,并在小鼠模型中加速伤口愈合。此外,ASCs 和成纤维细胞的转录组分析显示参与伤口愈合的过程被激活,并表明其安全性。源自 PDGF-BB 的新型肽被证明是一种安全的伤口愈合候选药物。我们还提出了一种用于新化合物初步筛选的多方面模型,这些新化合物可能在伤口愈合刺激中具有潜在用途。结果表明,源自 PDGF-BB 的肽是一种有前途的伤口治疗候选药物。