Mesenchymal stromal cells modulate infection and inflammation in the uterus and mammary gland

Abstract

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.

Mmp2 Deficiency Leads to Defective Parturition and High Dystocia Rates in Mice

“…Prior to that, females were treated with Depo-Provera (Pfizer Inc., New York City, NY, USA), which contains medroxyprogesterone acetate (MPA), for synchronization into diestrus stage. Diestrus stage was chosen according to our previous studies and experience [66]. The MPA (3 mg per mouse) was subcutaneously injected once on day 1 and a second time on day 5.…”

The use of stem cells in the treatment of mastitis in dairy cows

“…Then MSCs promote the T lymphocytes proliferation and the migration of Th17 cells 9 . The first such experiments concerned the use of fetal bovine MSCs (FBSC) 10 , and more recently, MSCs have also been isolated from adipose tissue 11 and the umbilical cord 12 , 13 . This study describes the effectiveness of an allogeneic suspension of stem cells derived from bone marrow (BMSC) and adipose tissue (ADSC) in the treatment of subclinical udder inflammation in dairy cows.…”

Population characteristics of pathogenic Escherichia coli in puerperal metritis of dairy cows in Ningxia region of China: a systemic taxa distribution of virulence factors and drug resistance genes

“…It was reported that E. coli appeared in the uterus within a few days of postpartum cows, followed by C. necrophorum and Cryptobacterium septicum ( Jeon and Galvao, 2018 ). Numerous studies have revealed that E. coli was one of the most important pathogenic bacteria causing postpartum uterine infections in dairy cows ( Ma et al, 2018 ; Schouten et al, 2023 ). Though the random amplification of polymorphic DNA and 16S rRNA gene sequencing of uterine contents and vaginal secretions of dairy cows with puerperal metritis, Wang et al (2013) demonstrated that E. coli was predominant in both uterus and vagina.…”