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J Pediatr ; 164(5): 966-972.e6, 2014 May.
Article in English | MEDLINE | ID: mdl-24508444

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 ß1 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.


Subject(s)
Bronchopulmonary Dysplasia/prevention & control , Cord Blood Stem Cell Transplantation/methods , Mesenchymal Stem Cell Transplantation/methods , Biomarkers/metabolism , Bronchopulmonary Dysplasia/diagnosis , Bronchopulmonary Dysplasia/metabolism , Cord Blood Stem Cell Transplantation/adverse effects , Cytokines/metabolism , Feasibility Studies , Female , Hepatocyte Growth Factor/metabolism , Humans , Infant, Newborn , Infant, Premature , Logistic Models , Male , Mesenchymal Stem Cell Transplantation/adverse effects , Severity of Illness Index , Trachea/metabolism , Trachea/surgery , Transplantation, Homologous/adverse effects , Transplantation, Homologous/methods , Treatment Outcome , Vascular Endothelial Growth Factor A/metabolism
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