Koret School of Veterinary Medicine, Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, POB 12, Rehovot, 76100, Israel.
Department of Animal Sciences, Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, POB 12, Rehovot, 76100, Israel.
BMC Vet Res. 2023 Mar 30;19(1):64. doi: 10.1186/s12917-023-03616-1.
The use of mesenchymal stromal cells (MSCs) is emerging as an efficacious and safe treatment for many infectious and non-infectious inflammatory diseases in human and veterinary medicine. Such use could be done to treat mastitis and metritis, which are the most common disease conditions affecting dairy cows leading to considerable economic losses and reduced animal welfare. Currently, both disease conditions are commonly treated using local and systemic administration of antibiotics. However, this strategy has many disadvantages including low cure rates and the public health hazards. Looking for alternative approaches, we investigated the properties of MSCs using in-vitro mammary and endometrial cell systems and in-vivo mastitis and metritis murine model systems. In-vitro, co-culture of mammary and uterus epithelial cells constructed with NF-kB reporter system, the master regulator of inflammation, demonstrated their anti-inflammatory effects in response to.LPS. In vivo, we challenge animals with field strains of mammary and utero pathogenic Escherichia coli and evaluated the effects of local and systemic application of MSC in the animal models. Disease outcome was evaluated using histological analysis, bacterial counts and gene expression of inflammatory markers. We show that MSC treatment reduced bacterial load in metritis and significantly modulated the inflammatory response of the uterus and mammary gland to bacterial infection. Most notably are the immune modulatory effects of remotely engrafted intravenous MSCs, which open new avenues to the development of MSC-based cell-free therapies.
间充质基质细胞 (MSCs) 的应用在人类和兽医医学中作为一种有效且安全的治疗方法，正在被应用于许多传染性和非传染性炎症性疾病。这种应用可以用于治疗乳腺炎和子宫炎，这是影响奶牛的最常见疾病，会导致巨大的经济损失和动物福利降低。目前，这两种疾病通常通过局部和全身应用抗生素来治疗。然而，这种策略有许多缺点，包括治愈率低和公共卫生危害。为了寻找替代方法，我们使用体外乳腺和子宫内膜细胞系统以及体内乳腺炎和子宫炎的小鼠模型系统来研究 MSCs 的特性。在体外，使用 NF-kB 报告系统构建的乳腺和子宫上皮细胞共培养物，作为炎症的主要调节剂，证明了它们对 LPS 的抗炎作用。在体内，我们用乳腺和子宫致病性大肠杆菌的田间株系来挑战动物，并评估了 MSC 在动物模型中的局部和全身应用效果。通过组织学分析、细菌计数和炎症标志物的基因表达来评估疾病结果。我们表明，MSC 治疗可降低子宫炎中的细菌负荷，并显著调节子宫和乳腺对细菌感染的炎症反应。特别值得注意的是，静脉内移植的 MSC 的免疫调节作用，为开发基于 MSC 的无细胞治疗开辟了新途径。
