Evaluating Mechanically Engineered Stem Cell Exosomes for Treating Endometrial Injury: A Clinical Study
Evaluation of the Therapeutic Effects of Mechanically Engineered Umbilical Cord-Derived Stem Cell Exosomes on Endometrial Injury: A Prospective, Non-Randomized, Parallel-Controlled Clinical Study
1 other identifier
interventional
90
1 country
2
Brief Summary
The goal of this clinical trial is to evaluate if engineered mechanically umbilical cord-derived stem cell exosomes, or conventional umbilical cord -derived stem cell exosomes, can improve endometrial thickness in women with thin endometrium. The main questions it aims to answer are: Can exosomes delivered via subendometrial injection improve endometrial thickness or clinical pregnancy rates compared to PRP (platelet-rich plasma)? Are there significant differences in endometrial thickness between the two treatment groups? Researchers will compare the intervention groups, which one group receives mechanical exosomes and the other receives conventional esosomes via subendometrial injection, to the control group, which receives PRP via the same methods, to see if exosomes provide superior therapeutic effects. Participants will: Receive either mechanical exosomesor or conventional esosomes or PRP through subendometrial injection. Be monitored for changes in endometrial parameters.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Feb 2025
Typical duration for phase_1
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
February 21, 2025
CompletedFirst Submitted
Initial submission to the registry
March 18, 2025
CompletedFirst Posted
Study publicly available on registry
March 26, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 12, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
March 31, 2027
ExpectedMarch 26, 2025
March 1, 2025
4 months
March 18, 2025
March 19, 2025
Conditions
Outcome Measures
Primary Outcomes (1)
Endometrial thickness
The endometrial thickness under ultrasound is measured on the HCG trigger day, oocyte retrieval day, day of progesterone Initiationor or embryo transfer day using transvaginal ultrasound in the sagittal/long-axis plane of the uterus. The measurement is taken at the thickest point within a 1 cm range from the uterine fundus, from the basal membrane on one side, perpendicular across the endometrial cavity line to the basal membrane on the opposite side.
30-90days
Secondary Outcomes (1)
clinical pregnancy
1-6 months
Study Arms (3)
Mechanically Engineered Umbilical Cord Mesenchymal Stem Cell-Derived Exosome Group (ME-UCMSC-Exo)
EXPERIMENTALParticipants in this arm will receive hysteroscopically guided intra-endometrial injection of 1-1.5 mL mechanically engineered umbilical cord mesenchymal stem cell-derived exosomes (ME-UCMSC-Exo) containing approximately 5×10¹⁰ particles/mL during the proliferative phase (Day 3-7 of the menstrual cycle). The exosomes are obtained from mechanically preconditioned UC-MSC cultures, which are subjected to biomechanical stress during expansion to enhance regenerative properties. The study aims to evaluate the efficacy of ME-UCMSC-Exo in improving endometrial thickness and pregnancy outcomes in patients with thin endometrium secondary to intrauterine adhesions.
Conventional Umbilical Cord Mesenchymal Stem Cell-Derived Exosome Group (UCMSC-Exo)
EXPERIMENTALParticipants in this arm will receive hysteroscopically guided intra-endometrial injection of 1-1.5 mL conventional umbilical cord mesenchymal stem cell-derived exosomes (UCMSC-Exo) containing approximately 5×10¹⁰ particles/mL during the proliferative phase (Day 3-7 of the menstrual cycle). Unlike the ME-UCMSC-Exo group, these exosomes are obtained from standard UC-MSC cultures without mechanical stress preconditioning. This group serves as a comparator to determine whether mechanical preconditioning enhances exosome efficacy in endometrial regeneration and pregnancy outcomes.
Platelet-Rich Plasma (PRP) Control Group
ACTIVE COMPARATORParticipants in this arm will receive hysteroscopically guided intra-endometrial injection of 1-1.5 mL autologous PRP following standard PRP preparation protocols during the proliferative phase (Day 3-7 of the menstrual cycle). PRP contains growth factors such as platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), and transforming growth factor-beta (TGF-β), which have been shown to improve endometrial receptivity and pregnancy outcomes. This group serves as a positive control for assessing the efficacy of exosome-based therapies.
Interventions
Mechanically engineered umbilical cord mesenchymal stem cell-derived exosomes (ME-UCMSC-Exo) are isolated from umbilical cord-derived mesenchymal stem cells (UCMSCs) subjected to mechanical stress conditioning during in vitro expansion. This process enhances exosome yield, bioactivity, and regenerative capacity. The exosomes are purified via ultracentrifugation and characterized for size, protein markers, and RNA content. In this study, ME-UCMSC-Exo is administered via intra-endometrial injection under hysteroscopic guidance. Each participant in this intervention group will receive 1-1.5 mL of exosome solution (containing approximately5\*10\^10 particles/mL) per injection site during the proliferative phase (Day 3-7 of the menstrual cycle). The aim is to enhance endometrial thickness, receptivity, and pregnancy outcomes in patients with thin endometrium secondary to intrauterine adhesions.
Umbilical cord mesenchymal stem cell-derived exosomes (UCMSC-Exo) are obtained from standard cultured UCMSCs without mechanical stress preconditioning. These exosomes undergo identical purification and characterization procedures as ME-UCMSC-Exo but lack biomechanical priming. UCMSC-Exo is also administered intra-endometrially via hysteroscopic injection at a dose of 1-1.5 mL (5\*10\^10 particles/mL) per site.
Platelet-rich plasma (PRP) is an autologous biological preparation obtained from centrifuged whole blood. It contains a high concentration of growth factors, including platelet-derived growth factor (PDGF), transforming growth factor-beta (TGF-β), and vascular endothelial growth factor (VEGF), which promote endometrial regeneration. In this study, PRP will be administered via hysteroscopically guided intra-endometrial injection at a dose of 1-1.5 mL per injection site, following standard PRP preparation protocols. This group serves as a positive control for evaluating the efficacy of exosome-based therapies.
Eligibility Criteria
You may qualify if:
- Females aged 20-40 years (inclusive of boundary values);
- Normal ovarian reserve function (criteria: AFC ≥ 7, AMH \> 1.1 ng/mL);
- History of transcervical resection of adhesions (TCRA);
- Received PRP treatment after TCRA;
- At least one embryo transfer (ET) cycle in which they underwent standard ovarian stimulation (fresh cycle) or standard hormone replacement therapy (FET cycle), with an endometrial thickness of \<7 mm;
- Planned to continue IVF/ICSI/FET-assisted conception;
- Able to accept and adhere to treatment and follow-up and willing to sign an informed consent form.
You may not qualify if:
- Patients with severe systemic diseases, surgical contraindications, or cycle contraindications;
- Patients with reproductive tract infections, genital tuberculosis, pelvic inflammatory disease, or malignant tumors of reproductive organs;
- Patients with systemic diseases that cause uterine bleeding;
- Patients allergic to any drugs, materials, or components used in this study;
- Patients at high risk for hormone-dependent tumors such as breast cancer or ovarian tumors;
- Patients with untreated submucosal fibroids of any size (FIGO 0/I/II), uterine fibroids ≥5 cm (FIGO III, IV, V, VI, VII), adenomyosis, unicornuate uterus, bicornuate uterus, or endometrial polyps;
- Patients with hydrosalpinx ≥3 cm or hydrosalpinx of any size with significant vaginal discharge;
- Patients with ovarian endometriotic cysts (chocolate cysts) ≥4 cm;
- Patients who participated in other clinical trials within 3 months before surgery or during the study period;
- Patients unable to tolerate anesthesia;
- Patients with genetic abnormalities;
- Other patients deemed unsuitable for participation in this study by the investigator.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Tang-Du Hospitallead
- Xi'an Jiaotong Universitycollaborator
Study Sites (2)
Tang-Du Hospital
Xi'an, Shaanxi, 710038, China
Tang-Du Hospital
Xi'an, Shaanxi, 710038, China
Related Publications (6)
Zhang H, Zhu H, Feng J, Zhang Z, Zhang S, Wang Z, Sun L, Zhang W, Gao B, Zhang Y, Lin M. Reprogramming of Activated Pancreatic Stellate Cells via Mechanical Modulation of Transmembrane Force-sensitive N-cadherin Receptor. J Mol Biol. 2023 Jan 15;435(1):167819. doi: 10.1016/j.jmb.2022.167819. Epub 2022 Sep 8.
PMID: 36089055BACKGROUNDCheng B, Wan W, Huang G, Li Y, Genin GM, Mofrad MRK, Lu TJ, Xu F, Lin M. Nanoscale integrin cluster dynamics controls cellular mechanosensing via FAKY397 phosphorylation. Sci Adv. 2020 Mar 4;6(10):eaax1909. doi: 10.1126/sciadv.aax1909. eCollection 2020 Mar.
PMID: 32181337BACKGROUNDZhang Z, Sha B, Zhao L, Zhang H, Feng J, Zhang C, Sun L, Luo M, Gao B, Guo H, Wang Z, Xu F, Lu TJ, Genin GM, Lin M. Programmable integrin and N-cadherin adhesive interactions modulate mechanosensing of mesenchymal stem cells by cofilin phosphorylation. Nat Commun. 2022 Nov 11;13(1):6854. doi: 10.1038/s41467-022-34424-0.
PMID: 36369425BACKGROUNDZhang C, Zhu H, Ren X, Gao B, Cheng B, Liu S, Sha B, Li Z, Zhang Z, Lv Y, Wang H, Guo H, Lu TJ, Xu F, Genin GM, Lin M. Mechanics-driven nuclear localization of YAP can be reversed by N-cadherin ligation in mesenchymal stem cells. Nat Commun. 2021 Oct 28;12(1):6229. doi: 10.1038/s41467-021-26454-x.
PMID: 34711824BACKGROUNDSun H, Dong J, Fu Z, Lu X, Chen X, Lei H, Xiao X, Chen S, Lu J, Su D, Xiong Y, Fang Z, Mao J, Chen L, Wang X. TSG6-Exo@CS/GP Attenuates Endometrium Fibrosis by Inhibiting Macrophage Activation in a Murine IUA Model. Adv Mater. 2024 May;36(21):e2308921. doi: 10.1002/adma.202308921. Epub 2024 Apr 15.
PMID: 38588501BACKGROUNDZhang W, Tang R, Xiao X, Liu J, Li M, Wang X. A Comparative Study on the Efficacy of Subendometrial Versus Intrauterine Platelet-Rich Plasma Injections for Treating Intrauterine Adhesions: A Retrospective Cohort Study. J Minim Invasive Gynecol. 2025 Apr;32(4):378-385.e1. doi: 10.1016/j.jmig.2024.11.007. Epub 2024 Dec 4.
PMID: 39643206BACKGROUND
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
The Fourth Military Medical University
Air Force Military Medical University, China
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Associate Chief Physician
Study Record Dates
First Submitted
March 18, 2025
First Posted
March 26, 2025
Study Start
February 21, 2025
Primary Completion
June 12, 2025
Study Completion (Estimated)
March 31, 2027
Last Updated
March 26, 2025
Record last verified: 2025-03
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- CSR
- Time Frame
- Individual participant data will be available upon request starting 6 months after the publication of study results and will remain accessible for 3 years.
- Access Criteria
- Data access is limited to researchers conducting studies on endometrial regeneration and reproductive medicine. Researchers must submit a proposal detailing their intended data use. Approved applicants will receive access via a secure, password-protected platform under a formal data use agreement (DUA)
Data on primary outcome measures, including endometrial thickness and pregnancy rates, will be shared after study completion. Requests for data access can be made through the corresponding author or institutional repository.