Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Women with spontaneous preterm birth | Experimental | 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. |
|
| Women with medically induced preterm birth | Active Comparator | 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. |
|
| Healthy women with at least two previous uncomplicated pregnancies | Active Comparator | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Venous blood sampling | Other | Venous blood sampling (3 mL) via venipuncture from the antecubital fossa at the time of delivery |
|
| Measure | Description | Time Frame |
|---|---|---|
| Anti-inflammatory effects of conditioned medium | To investigate the effect of CM-hAMSC on NLRP3 activation induced by lipopolysaccharide (LPS) and nigericin in cultured hAECs, hAMSCs, and PBMCs | Through study completion, an average of 1 year |
| Measure | Description | Time Frame |
|---|---|---|
| Inflammasome activation | 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. | Through study completion, an average of 1 year |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Chiara Tersigni, MD | Fondazione Policlinico Universitario Agostino Gemelli IRCCS | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Fondazione Policlinico Universitario A. Gemelli IRCCS, UOC Ostetricia e Patologia Ostetrica | Rome | Lazio | 00168 | Italy |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D047928 | Premature Birth |
| ID | Term |
|---|---|
| D007752 | Obstetric Labor, Premature |
| D007744 | Obstetric Labor Complications |
| D011248 | Pregnancy Complications |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
Not provided
Not provided
| ID | Term |
|---|---|
| D001800 | Blood Specimen Collection |
| D017218 | Cordocentesis |
| ID | Term |
|---|---|
| D013048 | Specimen Handling |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
Not provided
Not provided
This study is interventional because of maternal peripheral blood sampling
Not provided
Not provided
Not provided
Not provided
| Tissues sampling | Other | Sampling of the placenta and amniochorionic membranes (hAM) at delivery |
|
| Umbilical cord blood sampling | Other | Umbilical cord blood sampling from the residual cord attached to the placenta immediately after clamping. |
|
| D000091642 | Urogenital Diseases |
| D011677 | Punctures |
| D013514 | Surgical Procedures, Operative |
| D008919 | Investigative Techniques |
| D019152 | Paracentesis |
| D013812 | Therapeutics |