Volkova Marina V, Boyarintsev Valery V, Trofimenko Alexander V, Kovaleva Elena V, Othman Aya Al, Melerzanov Alexander V, Filkov Gleb I, Rybalkin Sergey P, Durymanov Mikhail O
Moscow Institute of Physics and Technology (National Research University), Institutsky per. 9, Dolgoprudny, Moscow Region 141701, Russia.
Research Center of Toxicology and Hygienic Regulation of Biopreparations, NRC Institute of Immunology FMBA of Russia, Ul. Lenina 102A, Dashkovka, Serpukhov district, Moscow Region 142253, Russia.
Burns. 2023 Mar;49(2):432-443. doi: 10.1016/j.burns.2022.04.014. Epub 2022 Apr 27.
Frostbite is a traumatic injury of the tissues upon low temperature environment exposure, which is characterized by direct cell injury due to freezing-thawing followed by development of an acute inflammatory process. Severe frostbite can lead to necrosis of soft tissues and loss of a limb. Mesenchymal stromal cells (MSCs) have a unique ability to modulate pathogenic immune response by secretion of paracrine factors, which suppress inflammation and mediate more efficient tissue regeneration. It should be noted that potential of stem cell therapy for frostbite injury treatment has not been investigated so far. Here, we evaluated a healing capacity of bone-marrow derived MSCs for the treatment of contact frostbite injury wound in a rat model.
Cold-contact injury in a Wistar rat model was induced by 1-minute tight application of the cooled probe (-196 ⁰C) to the skin surface of the left hip. Rat bone marrow MSCs were phenotypically characterized and used for local injections into non-damaged tissues surrounding the wound of animals from the experimental group. The second group of rats was treated in the same manner with 1 mL of isotonic sodium chloride solution. Analysis of cytokine and growth factor expression profile in сold-contact injury wounds was performed on days 5, 9, and 16 using immunoblotting and enzyme-linked immunosorbent assay. Animal recovery in MSC-treated and vehicle-treated groups was evaluated by several criteria including body weight recording, determination of eschar desquamation and re-epithelialization terms, assessment of wound closure kinetics, and histological scoring of the wounds on day 23.
It turned out that a single subcutaneous administration of MSCs around the wound site resulted in elevated expression of pro-survival and pro-angiogenic VEGF-A and PDGF and 3-5-fold decrease in pro-inflammatory IL-1β as compared with the frostbite wound treated with a vehicle. Moreover, treatment with MSCs caused accelerated wound re-epithelialization (p < 0.05) as well as a better histological score of the MSC-treated wounds.
Thus, our data suggested that the use of MSCs is a promising therapeutic strategy for the treatment of cold-induced injury wounds.
冻伤是机体在低温环境下暴露所致的创伤性损伤，其特征是冻融导致细胞直接损伤，随后发展为急性炎症过程。严重冻伤可导致软组织坏死和肢体缺失。间充质基质细胞（MSCs）具有通过分泌旁分泌因子调节致病性免疫反应的独特能力，这些因子可抑制炎症并介导更有效的组织再生。应当指出，迄今为止尚未研究干细胞疗法治疗冻伤损伤的潜力。在此，我们评估了骨髓源性间充质基质细胞在大鼠模型中治疗接触性冻伤损伤伤口的愈合能力。
通过将冷却探头（-196℃）紧密贴敷于Wistar大鼠左髋皮肤表面1分钟，诱导其冷接触损伤。对大鼠骨髓间充质基质细胞进行表型鉴定，并用于向实验组动物伤口周围的未损伤组织进行局部注射。第二组大鼠以相同方式用1 mL等渗氯化钠溶液治疗。在第5天、第9天和第16天，使用免疫印迹和酶联免疫吸附测定法分析冷接触损伤伤口中细胞因子和生长因子的表达谱。通过包括记录体重、确定焦痂脱落和再上皮化时间、评估伤口闭合动力学以及在第23天对伤口进行组织学评分等多项标准，评估间充质基质细胞治疗组和载体治疗组动物的恢复情况。
结果表明，与载体治疗的冻伤伤口相比，在伤口部位单次皮下注射间充质基质细胞导致促生存和促血管生成的血管内皮生长因子-A（VEGF-A）和血小板衍生生长因子（PDGF）表达升高，促炎白细胞介素-1β降低3至5倍。此外，间充质基质细胞治疗导致伤口再上皮化加速（p < 0.05），并且间充质基质细胞治疗的伤口组织学评分更好。
因此，我们的数据表明，使用间充质基质细胞是治疗冷诱导损伤伤口的一种有前景的治疗策略。
