MSC Exosome Therapy for Post-Preeclampsia Endothelial Dysfunction
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Mesenchymal Stem Cell-Derived Exosomes, Placebo (Sterile Saline Solution).
- Who it may be relevant to
- Registry conditions: Preeclampsia, Postpartum, Endothelial Injury, Exosome Multiomics. Basic parameters: 18 years — 50 years · Female.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Indonesia
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
Official title
The Effectiveness of Mesenchymal Stem Cell-Derived Exosome Therapy in Improving Endothelial Dysfunction in Postpartum Mothers With a History of Preeclampsia
Overview
\--- Why Is This Study Being Done? Women who have preeclampsia during pregnancy face a much higher risk of heart disease later in life. Preeclampsia is a serious pregnancy condition that causes high blood pressure and damages blood vessels. Even after the baby is born, the blood vessels do not fully heal on their own, which can lead to heart problems/cardiovascular years later. This study tests whether a new treatment called exosomes can help repair damaged blood vessels in women who had preeclampsia. Exosomes are tiny particles that come from stem cells and contain healing substances that may help blood vessels work better. \--- What Will Happen in This Study? This study will include 80 women who recently gave birth and had preeclampsia during their pregnancy. Half of the women will receive the exosome treatment through an IV, and half will receive a placebo (a substance with no active treatment). \--- What Will Participants Need to Do? Participants will: * Have blood tests and other health checks * Receive one treatment through an IV * Return for follow-up visits at 1 week after treatment * Have tests to check how well their blood vessels are working Who Can Join This Study? Women who: * Recently gave birth (within 1-2 weeks) * Had preeclampsia during their last pregnancy * Are healthy enough to participate * Can give permission to join the study What Are the Possible Benefits and Risks? The treatment may help repair blood vessel damage and reduce the risk of future heart disease. The exosome treatment appears to be safe based on other studies, but like any medical treatment, there may be side effects. \--- How Long Will the Study Last? The main treatment happens during one visit, with follow-up visits for 1 week to check on participants' health and see if the treatment is working. This research may lead to new ways to protect women's heart health after pregnancy complications.
Detailed description
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Background and Rationale
Preeclampsia affects 3-5% of pregnancies globally and represents a severe pregnancy-specific syndrome characterized by widespread maternal endothelial dysfunction. The pathophysiology involves abnormal trophoblast invasion leading to placental ischemia. Beyond immediate perinatal risks, preeclampsia carries devastating long-term cardiovascular consequences, with women experiencing a four-fold increased risk of heart failure, a 2.5-fold increased risk of coronary heart disease, and a two-fold increased risk of stroke and cardiovascular death. Moreover, post-cesarean postpartum mothers with a history of preeclampsia face particularly elevated risks, with cesarean delivery increasing postpartum preeclampsia risk by two- to seven-fold compared to vaginal delivery. This increased risk stems from altered hemodynamics, surgical stress responses, and compromised vascular integrity following cesarean procedures.
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Scientific Innovation
This study represents a paradigm shift from symptomatic management to active regenerative therapy using mesenchymal stem cell-derived exosomes (MSC-Exos). MSC-Exos offer several advantages over traditional approaches: natural tropism for vascular tissues, multi-pathway targeting capabilities, reduced immunogenicity compared to cell-based therapies, and superior circulation stability. Recent systematic reviews demonstrate favorable safety profiles with a low incidence of serious adverse events (0.7%).
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Intervention Details
Participants will receive a single intravenous or intramuscular dose of MSC-derived exosomes obtained from fetal adipose stem cells (ASC), produced under Good Manufacturing Practice (GMP) conditions. The exosomes contain bioactive cargo including growth factors, cytokines, proteins, and therapeutic microRNAs (particularly miR-126-3p) that mediate intercellular communication and tissue repair. Control participants will receive sterile saline solution of identical volume via the same route.
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Biomarker Strategy
The study employs miR-126-3p as the primary biomarker based on its exceptional diagnostic performance for endothelial dysfunction. miR-126-3p demonstrates high sensitivity (85.71%) and specificity (81.82%) with an area under the curve (AUC) of 0.792 for detecting endothelial dysfunction. This microRNA serves dual roles as both a pathological mediator and therapeutic target, making it ideal for monitoring treatment response. miR-126-3p is significantly downregulated in preeclampsia and directly regulates key angiogenic pathways including PI3K/AKT and MAPK/ERK signaling.
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Mechanistic Rationale
MSC-derived exosomes promote endothelial repair through multiple complementary mechanisms:
* Anti-inflammatory effects by promoting M2 macrophage polarization and reducing pro-inflammatory cytokines (IL-1β, IL-6, TNF-α). * Angiogenic promotion through delivery of pro-angiogenic factors including VEGF, VEGFR-2, and specific microRNAs. * Anti-apoptotic activity protecting endothelial cells via regulation of Bcl-2/Bax/Caspase-3 pathways. * Vascular barrier protection by maintaining intercellular junctions and preventing vascular permeability.
Clinical Assessment Protocol
The study incorporates comprehensive clinical monitoring including Hematology examination (Hemoglobin, MCV \& MCHC, Hematocrit, Leukocyte, Platelets), Vital Signs Assessment (Blood Pressure, Respiratory Rate, Heart Rate), Edema assessment (Upper Extremity Edema, Lower Extremity Edema, Facial Edema), proteinuria evaluation, and Imaging Outcome (Pulsatility Index (PI), and Resistance Index (RI) Uterine Artery, Uterine Involusion)
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Therapeutic Window and Follow-Up
The intervention targets the critical postpartum period (first-second week) when endothelial regeneration naturally occurs but may be compromised in preeclampsia patients. The 24-month follow-up period aligns with evidence suggesting therapeutic interventions during early postpartum may help reset long-term cardiovascular risk trajectories. This extended monitoring allows assessment of sustained therapeutic effects and long-term cardiovascular protection.
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Statistical Considerations
Sample size calculation (n=40 per group) is based on power analysis with α=0.05 and 80% power, accounting for a 10% dropout rate. The study design incorporates interim analysis at 50% recruitment with predetermined safety stopping rules monitored by an independent Data Safety Monitoring Board.
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Expected Clinical Impact
This study could establish a new therapeutic paradigm for postpartum care, shifting from reactive symptomatic management to proactive regenerative intervention. Success would provide the foundation for developing standardized exosome therapy protocols, potentially reducing long-term cardiovascular disease burden in high-risk postpartum populations, and contributing to improved maternal health outcomes with significant economic implications for healthcare systems.
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Regulatory and Safety Framework
The study operates under comprehensive ethical oversight with approval from the institutional Health Research Ethics Committee. Safety monitoring includes comprehensive adverse event reporting protocols and predefined safety stopping criteria to ensure participant protection throughout the study duration.
Interventions
- Biological Mesenchymal Stem Cell-Derived Exosomes
Mesenchymal stem cell-derived exosomes isolated from adipose-derived stem cells (ASC). The exosomes contain bioactive molecules including microRNAs (particularly miR-126-3p), proteins, and lipids that promote endothelial repair and regeneration. The product is manufactured under GMP conditions and administered as a single Intravenous or Intramuscular infusion. - Other Placebo (Sterile Saline Solution)
Sterile saline solution (0.9% sodium chloride) administered Intravenous or Intramuscular as placebo control. The volume and administration method are identical to the active treatment to maintain blinding.
Primary outcome measures
- Change in Endothelial Function Biomarker (miR-126-3p) [Time frame: Baseline and 1 week post-intervention]
Secondary outcome measures (12)
- Systolic Blood Pressure [Time frame: Baseline, first week, and 1 week post-intervention]
- Diastolic Blood Pressure [Time frame: Baseline, first week, and 1 week post-intervention]
- Hemoglobin Level [Time frame: Baseline and 1 week post-intervention]
- Hematocrit Level [Time frame: Baseline and 1 week post-intervention]
- Leukocyte Count [Time frame: Baseline and 1 week post-intervention]
- Platelet Count [Time frame: Baseline and 1 week post-intervention]
- Mean Corpuscular Volume (MCV) [Time frame: Baseline and 1 week post-intervention]
- Mean Corpuscular Hemoglobin Concentration (MCHC) [Time frame: Baseline and 1 week post-intervention]
- Proteinuria Level [Time frame: Baseline and 1 week post-intervention]
- Uterine Artery Pulsatility Index (PI) [Time frame: Baseline and 1 week post-intervention]
- Uterine Artery Resistance Index (RI) [Time frame: Baseline and 1 week post-intervention]
- Heart Rate [Time frame: Baseline, first week, and 1 week post-intervention]
Eligibility criteria
Inclusion criteria
- Postpartum
- Confirmed diagnosis of preeclampsia in the last pregnancy
- Postpartum period of first week and second week
- Able to provide informed consent
Exclusion criteria
- History of chronic hypertension prior to pregnancy
- Major cardiovascular disease history
- Active systemic infection
- Endothelial Injury history
- Active smoking status including vape, alcohol, drug addiction.
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Randomized
- Model
- Parallel assignment
- Masking
- Open label
- Primary purpose
- Treatment
Study locations
Indonesia · 1 center
- Dr. Hasan Sadikin Central General Hospital — Bandung
Publications
- Vioretti, R., Khairani, A. F., Fauziah, P. N., & Hilmanto, D. (2018). An evaluation of soyghurt potential on tumor necrosis factor-α and soluble endoglin levels in preclampsia maternal serum-induced placental trophoblast cell in vitro. International Food Research Journal, 25(4), 1397-1402.
- Gurnadi, J. I., Mose, J. C., Handono, B., Fauziah, P. N., & Pramatirta, A. Y. (2015). Correlation between fms-Like tyrosine kinase-1 (sFlt-1) cell-free messenger RNA expression and fms-Like tyrosine kinase-1 (sFlt-1) protein level in severe preeclampsia and normal pregnancy. International Journal of Integrated Health Sciences, 3(2), 66-71.
- Pramatirta AY, Mose J, Effendi JS, Krisnadi SR, Anwar AD, Fauziah PN, Gurnadi JI, Rihibiha DD. Correlation between cell-free mRNA expressions and PLGF protein level in severe preeclampsia. BMC Res Notes. 2015 Jun 2;8:208. doi: 10.1186/s13104-015-1186-9. PMID 26032325
Identifiers
NCT: NCT07183384 · OBGY-202508.01