Allogenic mesenchymal stem cell-conditioned medium does not affect sperm parameters and mitigates early endometrial inflammatory responses in mares

Tongu, Eriky Akio de Oliveira; Segabinazzi, Lorenzo G.T.M.; Alvarenga, Márcia Regina Martins; Monteiro, Aldine; Papa, Frederico Ozanam; Alvarenga, Marco Antônio

doi:10.1016/j.theriogenology.2021.03.019

Cited by 8 publications

(5 citation statements)

References 57 publications

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“…The observed effects are probably due to vesicle internalization by the endometrial epithelial cells of the treated mares, as supported by the in vitro study conducted by Perrini et al [ 39 ]. The reported data are also consistent with the results of Tongu et al [ 35 ] on MSC-CM.…”

Section: Discussionsupporting

confidence: 92%

“…Previous studies have shown how the intrauterine administration of MSC-CM reduces insemination-induced inflammation both in resistant [ 18 ] and susceptible mares [ 35 ]. After this treatment, the concentrations of anti-inflammatory IL-10 increased, while the levels of pro-inflammatory IL-6 decreased.…”

Section: Discussionmentioning

confidence: 99%

“…Corradetti et al (2014) demonstrated that AMSC-conditioned medium (AMSC-CM) was effective in the replenishment of endometrial cells and uterine regeneration [ 28 ]. To date, only one study has evaluated the in vivo effects of MSC-CM intrauterine infusion on mares susceptible to PPBIE, showing the effective downregulation of pro-inflammatory IL-6 and the upregulation of anti-inflammatory IL-10 in the uterine endometrium, as well as the reduction in PMN infiltration 6 h post-insemination [ 35 ].…”

Section: Introductionmentioning

confidence: 99%

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Amniotic Mesenchymal-Derived Extracellular Vesicles and Their Role in the Prevention of Persistent Post-Breeding Induced Endometritis

Consiglio

Gaspari

Funghi³

et al. 2023

IJMS

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Persistent post-breeding induced endometritis (PPBIE) is considered a major cause of subfertility in mares. It consists of persistent or delayed uterine inflammation in susceptible mares. There are many options for the treatment of PPBIE, but in this study, a novel approach aimed at preventing the onset of PPBIE was investigated. Stallion semen was supplemented with extracellular vesicles derived from amniotic mesenchymal stromal cells (AMSC-EVs) at the time of insemination to prevent or limit the development of PPBIE. Before use in mares, a dose–response curve was produced to evaluate the effect of AMSC-EVs on spermatozoa, and an optimal concentration of 400 × 106 EVs with 10 × 106 spermatozoa/mL was identified. At this concentration, sperm mobility parameters were not negatively affected. Sixteen susceptible mares were enrolled and inseminated with semen (n = 8; control group) or with semen supplemented with EVs (n = 8; EV group). The supplementation of AMSC-EVs to semen resulted in a reduction in polymorphonuclear neutrophil (PMN) infiltration as well as intrauterine fluid accumulation (IUF; p < 0.05). There was a significant reduction in intrauterine cytokine levels (p < 0.05) for TNF-α and IL-6 and an increase in anti-inflammatory IL-10 in mares in the EV group, suggesting successful modulation of the post-insemination inflammatory response. This procedure may be useful for mares susceptible to PPBIE.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Amniotic Mesenchymal-Derived Extracellular Vesicles and Their Role in the Prevention of Persistent Post-Breeding Induced Endometritis

Consiglio

Gaspari

Funghi³

et al. 2023

IJMS

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“…This potential use of MSC in cattle was recently discussed [7]. Some in-vitro and in-vivo studies demonstrated encouraging immunomodulating, antiinflammatory and antimicrobial effects in mammary and uterus cell systems and animal models [5,[8][9][10][11][12][13]. However, the feasibility and efficacy of MSC-based therapy for mastitis and metritis are still unknown and further research is required.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2023

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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.

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“…Even in the case of another type of inflammation, such as persistent post-breedinginduced endometritis (PPBIE), in this Special Issue, amniotic cells were proven to be effective in modulating inflammation by applying extracellular vesicles derived from amniotic mesenchymal stromal cells (AMSC-EVs) in stallion semen. To date, only one study has evaluated the in vivo effects of MSC-CM intrauterine infusion on mares that are susceptible to PPBIE [30], and another study showed that AMSC-conditioned medium (AMSC-CM) was effective in the replenishment of endometrial cells and uterine regeneration [31]. Lange-Consiglio and colleagues [32] demonstrated that the supplementation of AMSC-EVs to semen resulted in the successful modulation of post-insemination inflammatory responses in mares that could be able to prevent PPBIE.…”

mentioning

confidence: 99%

Amniotic Fluid and Placental Membranes as Sources of Stem Cells: Progress and Challenges 2.0

Maraldi,

Russo

2023

IJMS

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Allogenic mesenchymal stem cell-conditioned medium does not affect sperm parameters and mitigates early endometrial inflammatory responses in mares

Cited by 8 publications

References 57 publications

Amniotic Mesenchymal-Derived Extracellular Vesicles and Their Role in the Prevention of Persistent Post-Breeding Induced Endometritis

Amniotic Mesenchymal-Derived Extracellular Vesicles and Their Role in the Prevention of Persistent Post-Breeding Induced Endometritis

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

Amniotic Fluid and Placental Membranes as Sources of Stem Cells: Progress and Challenges 2.0

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