Clinical trial NCT06891508: The Placental Secretome as a Therapeutic Tool to Prevent Inflammation-induced Preterm Birth
Official title: The Placenta-derived Secretome of Mesenchymal Stromal Cells as a Therapeutic Tool to Prevent Inflammation-induced Preterm Birth
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Preterm Birth
Lead sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Sponsor class: OTHER
First posted: 2025-03-24
Enrollment: 60
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This study is interventional because of maternal peripheral blood sampling
Primary purpose: OTHER

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.

Eligibility criteria: 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

Primary outcomes:
measure: Anti-inflammatory effects of conditioned medium
timeFrame: Through study completion, an average of 1 year
Secondary outcomes:
measure: Inflammasome activation
timeFrame: Through study completion, an average of 1 year
Other outcomes:
Locations:
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario A. Gemelli IRCCS, UOC Ostetricia e Patologia Ostetrica
state: Lazio
Study officials:
affiliation: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
name: Chiara Tersigni, MD
role: PRINCIPAL_INVESTIGATOR
References: