Safety and Efficacy of Umbilical Cord-derived Mesenchymal Stem Cell(MSC) Transplantation in the Treatment of Bronchopulmonary Dysplasia(BPD) in Premature Infants (MSC，BPD)

Safety and Efficacy of Umbilical Cord-derived Mesenchymal Stem Cell Transplantation in the Treatment of Bronchopulmonary Dysplasia in Premature Infants

Bronchopulmonary dysplasia (BPD) is a chronic lung disease, which is a major complication of very low and ultra-low preterm infants. Moderate and severe BPD survivors are prone to adverse outcomes such as impaired lung function, childhood exercise intolerance, and neurodevelopmental retardation in the long term, which seriously affects their quality of life and brings a heavy burden to society and families. However, the pathogenesis of BPD is complex, including pulmonary vascular dysplasia, lung inflammation, and impaired alveolar development. There is currently no specific clinical drug to cure BPD. Mesenchymal stem cells (MSCs) are a kind of multipotent stem cells that exist in almost all organs and tissues of individuals. MSCs have the properties including self-renewal, multi-directional differentiation, and immunosuppressive and anti-inflammatory abilities. Preclinical studies have shown that MSCs can alleviate BPD by improving alveolar and pulmonary vascular development, and reducing pulmonary fibrosis. Several phase I clinical studies have demonstrated that intratracheal transplantation of human umbilical cord blood-derived mesenchymal stem cells for children with BPD is safe and feasible.

This study aims to further evaluate the safety and efficacy of umbilical cord-derived mesenchymal stem cell transplantation in the treatment of severe BPD in premature infants, in the hope of increasing the survival rate and improving the prognosis of severe BPD.

Study Overview

• Status: Recruiting
• Conditions: BPD - Bronchopulmonary Dysplasia
• Intervention / Treatment: Drug: MSC

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Yaoqin Hu, MD; Phone Number: 0571-86670704; Email: huyaoqin@zju.edu.cn

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310052
      • Recruiting
      • The Children's Hospital of Zhejiang University School of Medicine
      • Contact: Ruoqiong Huang, Postdoc; Phone Number: 0571-86670704; Email: huangruoqiong@zju.edu.cn
      • Principal Investigator: Qiang Shu, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 23-29 weeks of gestation, birth weight 500-1500g;
2. For patients with no improvement or aggravation of lung condition after DART hormone therapy, and positive pressure ventilation by tracheal intubation is still required at a correct gestational age of 36 weeks.
3. Children with severe BPD after early use of PS
4. Parents agree to participate in clinical trials.

Exclusion Criteria:

1. Premature infants not suitable for the given gestational age;
2. Other congenital structural malformations of trachea, bronchus and lungs;
3. Complicated with severe congenital heart disease;
4. Complicated with Periventricular Leukomalacia (PVL);
5. Complicated with intraventricular hemorrhage (IVH) above level 3;
6. Septic shock or positive blood culture;
7. Acute pulmonary hemorrhage;
8. Intracranial and extracranial diseases affecting respiratory rate and rhythm.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MSC transplantation; MSCs (1×10^7/kg) are administered intratracheally to participators.	Drug: MSC; Intratracheal administration of umbilical cord-derived mesenchymal stem cells (MSCs).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Extubating time after MSC transplantation	Record how long it takes for the participants' tracheal tubes to be removed after MSC transplantation.	until 24 months of corrected age
The number of times and total duration of re-intubation after extubating	If the participants' tracheal tubes are removed after MSC transplantation, record the number of times and total duration of tracheal re-intubation until discharge and 24 months of corrected age.	until 24 months of corrected age
Mortality of BPD	Record the number of participants who died from BPD.	until 24 months of corrected age

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Further assess the severity of BPD by detecting the levels of pro-inflammatory cytokine in alveolar lavage fluid, pulmonary function index and chest radiography.	The levels of pro-inflammatory cytokine (IL-6, IL-8, TNF-α, IL-1β, IL-10, MMP-9, TGF-β) in alveolar lavage fluid are examined via ELISA kits before and at 7 days after MSC transplantation. Record the pulmonary function index including FiO2, PaO2, VT, PEEP. Participants perform the chest radiography examination before and at 24 hours, 3 Days, 7days and 1month after MSC transplantation. The severity of BPD will be further assessed by above indicators.	until 24 months of corrected age
Short-term safety assessment of MSC transplantation by whether anaphylaxis and severe infection are observed within 24 hours after MSC transplantation.	Observed and record whether participants experience anaphylaxis including rash and anaphylactic shock within 24 hours after MSC transplantation. Also, record whether participants experience severe infection including hyperpyrexia, aggravated pulmonary inflammation and worse pulmonary function within 24 hours after MSC transplantation.	within 24 hours after MSC transplantation
long-term safety assessment of MSC transplantation by whether intraventricular hemorrhage, periventricular leukomalacia, neurodevelopmental problems and tumor formation are observed after MSC transplantation until 24 months of corrected age.	Participants perform the cranial ultrasound to assess whether intraventricular hemorrhage and periventricular leukomalacia occur. Cranial MRI and Bayley Scale for Infant Development (BSID) are performed to assess neurodevelopment. Ultrasound and MRI examinations are performed to assess tumor formation after MSC transplantation until 24 months of corrected age.	until 24 months of corrected age

Collaborators and Investigators

• Sponsor: The Children's Hospital of Zhejiang University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): August 9, 2024
• Primary Completion (Estimated): August 9, 2027
• Study Completion (Estimated): August 9, 2027

Study Registration Dates

• First Submitted: January 6, 2025
• First Submitted That Met QC Criteria: January 22, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 22, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: Premature infants; Bronchopulmonary dysplasia (BPD); Mesenchymal stem cells (MSCs)
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Premature, Diseases; Infant, Newborn, Diseases; Lung Injury; Ventilator-Induced Lung Injury; Hyperplasia; Bronchopulmonary Dysplasia
• Other Study ID Numbers: 2019-SC-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No