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Allogeneic human umbilical cord-derived mesenchymal stem cells for severe bronchopulmonary dysplasia in children: study protocol for a randomized controlled trial (MSC-BPD trial).

ABSTRACT: BACKGROUND:Bronchopulmonary dysplasia (BPD) is a complex lung pathological lesion secondary to multiple factors and one of the most common chronic lung diseases. It has a poor prognosis, especially in preterm infants. However, effective therapies for this disease are lacking. Stem-cell therapy is a promising way to improve lung injury and abnormal alveolarization, and the human umbilical cord (hUC) is a good source of mesenchymal stem cells (MSCs), which have demonstrated efficacy in other diseases. We hypothesized that intravenously administered allogeneic hUC-MSCs are safe and effective for severe BPD. METHODS:The MSC-BPD trial is a randomized, single-center, open-label, dose-escalation, phase-II trial designed to investigate the safety and efficacy of hUC-MSCs in children with severe BPD. In this study, 72 patients will be enrolled and randomly divided into two intervention groups and one control group. Patients in the intervention groups will receive a low dose of hUC-MSCs (n?=?24; 2.5 million cells/kg) or a high dose of hUC-MSCs (n?=?24; 5 million cells/kg) in combination with traditional supportive treatments for BPD. The patients in the control group (n?=?24) will be treated with traditional supportive treatments alone without hUC-MSCs. The primary outcome measures will be cumulative duration of oxygen therapy. Follow-up assessments will be performed at 1, 3, 6, 12, and 24?months post intervention, and the key outcome during follow-up will be changes on chest radiography. Statistical analyses will evaluate the efficacy of the hUC-MSC treatment. DISCUSSION:This will be the first randomized controlled trial to evaluate the safety and efficacy of intravenously administered hUC-MSCs in children with severe BPD. Its results should provide a new evidence-based therapy for severe BPD. TRIAL REGISTRATION:ClinicalTrials.gov, ID: NCT03601416. Registered on 26 July 2018.

SUBMITTER: Wu X

PROVIDER: S-EPMC6995070 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Allogeneic human umbilical cord-derived mesenchymal stem cells for severe bronchopulmonary dysplasia in children: study protocol for a randomized controlled trial (MSC-BPD trial).

Wu Xian X Xia Yunqiu Y Zhou Ou O Song Yan Y Zhang Xianhong X Tian Daiyin D Li Qubei Q Shu Chang C Liu Enmei E Yuan Xiaoping X He Ling L Liu Chengjun C Li Jing J Liang Xiaohua X Yang Ke K Fu Zhou Z Zou Lin L Bao Lei L Dai Jihong J

Trials 20200131 1

<h4>Background</h4>Bronchopulmonary dysplasia (BPD) is a complex lung pathological lesion secondary to multiple factors and one of the most common chronic lung diseases. It has a poor prognosis, especially in preterm infants. However, effective therapies for this disease are lacking. Stem-cell therapy is a promising way to improve lung injury and abnormal alveolarization, and the human umbilical cord (hUC) is a good source of mesenchymal stem cells (MSCs), which have demonstrated efficacy in oth ...[more]

PMID: 32005282

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Project description:Bronchopulmonary dysplasia (BPD) is the most common complication of prematurity and a key contributor to the large health care burden associated with prematurity, longer hospital stays, higher hospital costs, and frequent re-hospitalizations of affected patients through the first year of life and increased resource utilization throughout childhood. This disease is associated with abnormal pulmonary function that may lead to BPD-associated pulmonary hypertension (PH), a major contributor to neonatal mortality and morbidity. In the absence of any definitive treatment options, this life-threatening disease is associated with high resource utilization during and after neonatal intensive care unit (NICU) stay. The goal of this study was to test the safety and efficacy of a small molecule derivative of chitin, AVR-48, as prophylactic therapy for preventing experimental BPD in a mouse model. Two doses of AVR-48 were delivered either intranasally (0.11 mg/kg), intraperitoneally (10 mg/kg), or intravenously (IV) (10 mg/kg) to newborn mouse pups on postnatal day (P)2 and P4. The outcomes were assessed by measuring total inflammatory cells in the broncho-alveolar lavage fluid (BALF), chord length, septal thickness, and radial alveolar counts of the alveoli, Fulton's Index (for PH), cell proliferation and cell death by immunostaining, and markers of inflammation by Western blotting and ELISA. The bioavailability and safety of the drug were assessed by pharmacokinetic and toxicity studies in both neonatal mice and rat pups (P3-P5). Following AVR-48 treatment, alveolar simplification was improved, as evident from chord length, septal thickness, and radial alveolar counts; total inflammatory cells were decreased in the BALF; Fulton's Index was decreased and lung inflammation and cell death were decreased, while angiogenesis and cell proliferation were increased. AVR-48 was found to be safe and the no-observed-adverse-effect level (NOAEL) in rat pups was determined to be 100 mg/kg when delivered via IV dosing with a 20-fold safety margin. With no reported toxicity and with a shorter half-life, AVR-48 is able to reverse the worsening cardiopulmonary phenotype of experimental BPD and BPD-PH, compared to controls, thus positioning it as a future drug candidate.

Dataset Information

Allogeneic human umbilical cord-derived mesenchymal stem cells for severe bronchopulmonary dysplasia in children: study protocol for a randomized controlled trial (MSC-BPD trial).

Publications

Allogeneic human umbilical cord-derived mesenchymal stem cells for severe bronchopulmonary dysplasia in children: study protocol for a randomized controlled trial (MSC-BPD trial).

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