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.
Bibliographical noteFunding Information:
This work was supported by BARD grant number IS-5067–18 and by Israeli Dairy Board grant number 820–0341-18. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
The authors acknowledge the scientific and technical assistance in the construction and use of the lentivirus technologies from Drs. James Bagnall and Pawel Paszek of the Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom.
© 2023, The Author(s).
- Escherichia coli
- Mesenchymal stromal cells
- Murine model