Mesenchymal stem cells for bronchopulmonary dysplasia: phase 1 dose-escalation clinical trial
Yun Sil Chang, So Yoon Ahn, Hye Soo Yoo, Se In Sung, Soo Jin Choi, Won Il Oh, Won Soon Park, Yun Sil Chang, So Yoon Ahn, Hye Soo Yoo, Se In Sung, Soo Jin Choi, Won Il Oh, Won Soon Park
Abstract
Objective: To assess the safety and feasibility of allogeneic human umbilical cord blood (hUCB)-derived mesenchymal stem cell (MSC) transplantation in preterm infants.
Study design: In a phase I dose-escalation trial, we assessed the safety and feasibility of a single, intratracheal transplantation of hUCB-derived MSCs in preterm infants at high risk for bronchopulmonary dysplasia (BPD). The first 3 patients were given a low dose (1 × 10(7) cells/kg) of cells, and the next 6 patients were given a high dose (2 × 10(7) cells/kg). We compared their adverse outcomes, including BPD severity, with those of historical case-matched comparison group.
Results: Intratracheal MSC transplantation was performed in 9 preterm infants, with a mean gestational age of 25.3 ± 0.9 weeks and a mean birth weight of 793 ± 127 g, at a mean of 10.4 ± 2.6 days after birth. The treatments were well tolerated, without serious adverse effects or dose-limiting toxicity attributable to the transplantation. Levels of interleukin-6, interleukin-8, matrix metalloproteinase-9, tumor necrosis factor α, and transforming growth factor β1 in tracheal aspirates at day 7 were significantly reduced compared with those at baseline or at day 3 posttransplantation. BPD severity was lower in the transplant recipients, and rates of other adverse outcomes did not differ between the comparison group and transplant recipients.
Conclusion: Intratracheal transplantation of allogeneic hUCB-derived MSCs in preterm infants is safe and feasible, and warrants a larger and controlled phase II study.
Trial registration: ClinicalTrials.gov NCT01297205.
Copyright © 2014 The Authors. Published by Mosby, Inc. All rights reserved.
Source: PubMed