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

Institute of Hospitalization and Scientific Care (IRCCS)

Status: Active, not recruiting

Conditions: Preterm Birth

Treatments: Other: Tissues sampling; Other: Umbilical cord blood sampling; Other: Venous blood sampling

Study type: Interventional

Funder types: Other

Identifiers

NCT06891508

7273

Details and patient eligibility

About

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.

Full 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.

Enrollment: 60 estimated patients

Sex: Female

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Other

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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60 participants in 3 patient groups

Women with spontaneous preterm birth

Experimental group

Description:

Women enrolled in this study will undergo a venous blood draw (3 mL) via venipuncture from the antecubital fossa at the time of delivery. The placenta and amniochorionic membranes (hAM) will be collected within 30 minutes after delivery, performed via cesarean section. Additionally, a 3 mL sample of umbilical cord blood will be drawn from the residual cord attached to the placenta immediately after clamping.

Treatment:

Other: Venous blood sampling

Other: Umbilical cord blood sampling

Other: Tissues sampling

Women with medically induced preterm birth

Active Comparator group

Description:

Women enrolled in this study will undergo a venous blood draw (3 mL) via venipuncture from the antecubital fossa at the time of delivery. The placenta and amniochorionic membranes (hAM) will be collected within 30 minutes after delivery, performed via cesarean section. Additionally, a 3 mL sample of umbilical cord blood will be drawn from the residual cord attached to the placenta immediately after clamping.

Treatment:

Other: Venous blood sampling

Other: Umbilical cord blood sampling

Other: Tissues sampling

Healthy women with at least two previous uncomplicated pregnancies

Active Comparator group

Description:

Women enrolled in this study will undergo a venous blood draw (3 mL) via venipuncture from the antecubital fossa at the time of delivery. The placenta and amniochorionic membranes (hAM) will be collected within 30 minutes after delivery, performed via cesarean section. Additionally, a 3 mL sample of umbilical cord blood will be drawn from the residual cord attached to the placenta immediately after clamping.

Treatment:

Other: Venous blood sampling

Other: Umbilical cord blood sampling

Other: Tissues sampling