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INTRODUCTION: Lung injuries, such as bronchopulmonary dysplasia (BPD), remain a major complication of preterm birth, with limited therapeutic options. One potential emerging therapy is umbilical cord blood (UCB)-derived therapy. OBJECTIVES: To systematically assess the safety and efficacy of UCB-derived therapy for preterm lung injury in preclinical and clinical studies. METHODS: A systematic search of MEDLINE, Embase, CENTRAL, ClinicalTrials.gov, and WHO International Trials Registry Platform was performed. A meta-analysis was conducted with Review Manager (5.4.1) using a random effects model. Data was expressed as standardized mean difference (SMD) for preclinical data and pooled relative risk (RR) for clinical data, with 95% confidence intervals (CI). Potential effect modifiers were investigated via subgroup analysis. Certainty of evidence was assessed using the GRADE system. RESULTS: Twenty-three preclinical studies and six clinical studies met eligibility criteria. Statistically significant improvements were seen across several preclinical outcomes, including alveolarization (SMD, 1.32, 95%CI [0.99, 1.65]), angiogenesis (SMD, 1.53, 95%CI [0.87, 2.18]), and anti-inflammatory cytokines (SMD, 1.68, 95%CI [1.03, 2.34]). In clinical studies, 103 preterm infants have received UCB-derived therapy for preterm lung injury and no significant difference was observed in the development of BPD (RR, 0.93, 95%CI [0.73, 1.18]). Across both preclinical and clinical studies, administration of UCB-derived therapy appeared safe. Certainty of evidence was assessed as "low." CONCLUSIONS: Administration of UCB-derived therapy was associated with statistically significant improvements across several lung injury markers in preclinical studies. Early clinical studies demonstrated the administration of UCB-derived therapy as safe and feasible but lacked data regarding efficacy.
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INTRODUCTION: We have previously described preclinical literature which supports umbilical cord blood-derived cell (UCBC) therapy as an efficacious treatment for perinatal brain injury. However, efficacy of UCBCs may be influenced by different patient population and intervention characteristics. OBJECTIVES: To systematically review the effects of UCBCs on brain outcomes in animal models of perinatal brain injury across subgroups to better understand the contribution of model type (preterm versus term), brain injury type, UCB cell type, route of administration, timing of intervention, cell dosage, and number of doses. METHODS: A systematic search of MEDLINE and Embase databases was performed to identify studies using UCBC therapy in animal models of perinatal brain injury. Subgroup differences were measured by chi2 test where possible. RESULTS: Differential benefits of UCBCs were seen across a number of subgroup analyses including intraventricular hemorrhage (IVH) vs. hypoxia ischemia (HI) model (apoptosis white matter (WM): chi2 = 4.07; P = .04, neuroinflammation-TNF-α: chi2 = 5.99; P = .01), UCB-derived mesenchymal stromal cells (MSCs) vs. UCB-derived mononuclear cells (MNCs) (oligodendrocyte WM: chi2 = 5.01; P = .03, neuroinflammation-TNF-α: chi2 = 3.93; P = .05, apoptosis grey matter (GM), astrogliosis WM), and intraventricular/intrathecal vs. systemic routes of administration (microglial activation GM: chi2 = 7.51; P = .02, astrogliosis WM: chi2 = 12.44; P = .002). We identified a serious risk of bias and overall low certainty of evidence. CONCLUSIONS: Preclinical evidence suggests UCBCs to show greater efficacy in the injury model of IVH compared to HI, the use of UCB-MSCs compared to UCB-MNCs and the use of local administrative routes compared to systemic routes in animal models of perinatal brain injury. Further research is needed to improve certainty of evidence and address knowledge gaps.