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.

Clinical applications of mesenchymal stromal cell-based therapies for pulmonary diseases: An Update and Concise Review

“…The next Phase II clinical trial (NCT03392467) and follow-up (NCT04003857) for intratracheal instillation of UCMSCs to preterm infants with BPD are ongoing 78 , 79 . Recently, Wu et al 80 reported the first randomized, single-center, open-label, dose-escalation, Phase II trial (NCT03601416) using MSCs intravenously administered in children with severe BPD. In this study, the safety and efficacy of treatment with low- ( n =24, 2.5×10 6 cells/kg) and high-dose ( n =24, 5×10 6 cells/kg) intravenous infusions of allogeneic UCMSCs were compared with those of traditional supportive treatments for BPD.…”

Double face of stem cells in paediatrics: therapeutic applications of mesenchymal stem cells and threats from cancer stem cells

“…Studies show that MSCs therapy is beneficial in the treatment of BPD in rodent models, where it promotes angiogenesis, improve alveolarisation and pulmonary hypertension (25)(26)(27) . Data from clinical trials in prematurely born infants at a risk of BPD and children with severe BPD have demonstrated that the umbilical cord-derived MSCs are beneficial (28)(29)(30) . Moreover, limited clinical data indicate that transplanted stem cells can be neuroprotective, and may decrease inflammatory injury in preterm neonates, neonatal stroke, and cerebral palsy (31) .…”

Mesenchymal Stromal Cells for the Treatment of Interstitial Lung Disease in Children: A Look from Pediatric and Pediatric Surgeon Viewpoints

“…Stem cell therapy represents a prospective approach in regenerative medicine for the repair, replacement, and rejuvenation of tissue [ 1 , 2 ]. Mesenchymal stromal cells (MSCs) expanded in vitro have been proposed as potential therapy to treat congenital and acquired lung diseases [ 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 ]. MSCs are multipotent cells that can differentiate into multiple tissue-forming cell lineages, such as osteoblasts, adipocytes, chondrocytes, tenocytes, and myocytes.…”