The Placental Secretome as a Therapeutic Tool to Prevent Inflammation-induced Preterm Birth

Not Applicable

Active, not recruiting

• Conditions: Preterm Birth

• Registration Number: NCT06891508
• Lead Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS

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.

Study Timeline

• Status Verified: 2025-03
• Study Start: 2025-03-11
• Study First Submitted: 2025-03-11
• Study First Submitted QC: 2025-03-17
• Last Update Submitted: 2025-03-17
• Study First Posted: 2025-03-24
• Last Update Posted: 2025-03-24
• Primary Completion: 2026-03-20
• Study Completion: 2028-03-20

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: Female
• Target Recruitment: 60

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.

Trial Locations

Locations (1)

Fondazione Policlinico Universitario A. Gemelli IRCCS, UOC Ostetricia e Patologia Ostetrica; 🇮🇹 Roma, Lazio, Italy