Preterm Birth
Conditions
Brief summary
Preterm birth complicates 10% of all pregnancies and is the leading cause of perinatal morbidity and mortality worldwide. Intra-amniotic inflammation (IAI) and chorioamnionitis are well-established causes of PTB; however, a treatable infectious trigger is identified in only 50% of cases.In sterile IAI and/or preterm premature rupture of membranes (pPROM), there are currently no effective therapeutic options to reduce inflammation, promote amniotic sac healing, and prevent preterm birth. Growing evidence suggests that the secretome of mesenchymal stem cells (MSC) exhibits immunomodulatory and tissue-regenerative properties, making it a promising therapeutic tool for inflammatory disorders. Specifically, the conditioned medium from human amniotic mesenchymal stromal cells (CM-hAMSC) has been successfully used to treat various preclinical inflammatory disease models. The aims of this study will be:1) to evaluate the activation of the NLRP3 inflammasome in hAM cells and peripheral blood mononuclear cells (PBMCs) from women with PTB. 2)To investigate the effect of CM-hAMSC on NLRP3 activation induced by lipopolysaccharide (LPS) and nigericin in cultured human amniotic epithelial cells (hAECs), amniotic mesenchymal stromal cells (hAMSCs), and PBMCs.
Detailed description
Preterm birth complicates 10% of all pregnancies and is the leading cause of perinatal morbidity and mortality worldwide. Among all PTB cases, 70% occur spontaneously (SPTB), while the remaining 30% are medically indicated due to severe intrauterine growth restriction (IUGR). Intra-amniotic inflammation (IAI) and chorioamnionitis are well-established causes of SPTB; however, a treatable infectious trigger is identified in only 50% of cases.In sterile IAI and/or preterm premature rupture of membranes (pPROM), there are currently no effective therapeutic options to reduce inflammation, promote amniotic sac healing, and prevent preterm birth.Recent studies have identified the activation of the NLRP3 inflammasome in human amniotic membranes (hAM) as a key mechanism in the pathogenesis of SPTB. Targeting NLRP3 as a therapeutic approach for inflammatory diseases is rapidly advancing. Growing evidence suggests that the secretome of mesenchymal stem cells (MSC) exhibits immunomodulatory and tissue-regenerative properties, making it a promising therapeutic tool for inflammatory disorders. Specifically, the conditioned medium from human amniotic mesenchymal stromal cells (CM-hAMSC) has been successfully used to treat various preclinical inflammatory disease models. The aims of this study will be:1) to evaluate the activation of the NLRP3 inflammasome in hAM cells and peripheral blood mononuclear cells (PBMCs) from women with PTB. 2)To investigate the effect of CM-hAMSC on NLRP3 activation induced by lipopolysaccharide (LPS) and nigericin in cultured human amniotic epithelial cells (hAECs), amniotic mesenchymal stromal cells (hAMSCs), and PBMCs.
Interventions
Venous blood sampling (3 mL) via venipuncture from the antecubital fossa at the time of delivery
OTHERTissues sampling
Sampling of the placenta and amniochorionic membranes (hAM) at delivery
Umbilical cord blood sampling from the residual cord attached to the placenta immediately after clamping.
Sponsors
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Intervention model description
This study is interventional because of maternal peripheral blood sampling
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Full-term uncomplicated pregnancy, without any medical conditions or ongoing pharmacological treatment (control group). * Pregnancy complicated by spontaneous preterm birth (gestational age 24-32 weeks). * Pregnancy complicated by medically indicated preterm birth (gestational age 24-32 weeks).
Exclusion criteria
* Age \<18 years * Chronic infections (HIV or HCV) * Cancer * Multiple pregnancy * Inability to provide informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Anti-inflammatory effects of conditioned medium | Through study completion, an average of 1 year | To investigate the effect of CM-hAMSC on NLRP3 activation induced by lipopolysaccharide (LPS) and nigericin in cultured hAECs, hAMSCs, and PBMCs |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Inflammasome activation | Through study completion, an average of 1 year | To assess NLRP3 inflammasome activation in hAM cells and peripheral blood mononuclear cells (PBMCs) from women with term or preterm birth, whether spontaneous or medically indicated. |
Countries
Italy
Outcome results
None listed