Department of Pharmacognosy, Faculty of Pharmacy, Deraya University, Minia 61111, Egypt.
Department of Pharmacology, Faculty of Pharmacy, Deraya University, Minia 61111, Egypt.
Mar Drugs. 2023 May 30;21(6):336. doi: 10.3390/md21060336.
Impaired skin wound healing is still a major challenge, especially with immunocompromised patients who express delayed healing and are susceptible to infections. Injection of rat-derived bone marrow mesenchymal stem cells (BMMSCs) via the tail vein accelerates cutaneous wound healing via their paracrine activity. The present work aimed to investigate the combined wound-healing potential of BMMSCs and algae extract in immunocompromised rats. High-resolution liquid chromatography-mass spectrometry (HR-LC-MS) investigation of the extract revealed the presence of variant phytochemicals, mostly phenolics, and terpenoids, known for their angiogenic, collagen-stimulating, anti-inflammatory, and antioxidant properties. The BMMSCs were isolated and characterized for CD markers, where they showed a positive expression of CD90 by 98.21% and CD105 by 97.1%. Twelve days after inducing immunocompromise (40 mg/kg hydrocortisone daily), a circular excision was created in the dorsal skin of rats and the treatments were continued for 16 days. The studied groups were sampled on days 4, 8, 12, and 16 after wounding. The gross/histopathological results revealed that the wound closure (99%), thickness, density of new epidermis and dermis, and skin elasticity in the healed wounds were considerably higher in the BMMSCs/ group than the control group ( < 0.05). RT-PCR gene expression analysis revealed that the BMMSCs/ extract combination had perfectly attenuated oxidative stress, proinflammatory cytokines, and activation at day 16 of wounding. The combination holds promise for regenerative medicine, representing a revolutionary step in the wound healing of immunocompromised patients, with still a need for safety assessments and further clinical trials.
皮肤创伤愈合受损仍然是一个主要挑战，尤其是对于免疫功能低下的患者，他们表现出愈合延迟且易感染。通过尾静脉注射大鼠来源的骨髓间充质干细胞（BMMSCs）可通过旁分泌作用加速皮肤创伤愈合。本研究旨在探究 BMMSCs 与藻类提取物在免疫功能低下大鼠中的联合创伤愈合潜能。通过高分辨液相色谱-质谱联用（HR-LC-MS）对提取物进行分析，发现其存在多种植物化学物质，主要为酚类和萜类物质，具有促进血管生成、刺激胶原蛋白、抗炎和抗氧化作用。对 BMMSCs 进行 CD 标志物鉴定，发现其 CD90 阳性表达率为 98.21%，CD105 阳性表达率为 97.1%。在诱导免疫功能低下（每天 40mg/kg 氢化可的松） 12 天后，在大鼠背部皮肤创建一个圆形切除伤口，并继续治疗 16 天。在创伤后第 4、8、12 和 16 天对研究组进行采样。大体/组织病理学结果显示，BMMSCs/ 组的伤口闭合（99%）、厚度、新生表皮和真皮密度以及愈合伤口的皮肤弹性均显著高于对照组（ < 0.05）。RT-PCR 基因表达分析显示，BMMSCs/提取物联合应用可完美减轻创伤后第 16 天的氧化应激、促炎细胞因子和激活。该联合疗法有望应用于再生医学，代表着免疫功能低下患者创伤愈合领域的革命性进步，仍需要进行安全性评估和进一步的临床试验。
