Are all stem cells equal? Systematic review, evidence map, and meta-analyses of preclinical stem cell-based therapies for bronchopulmonary dysplasia

Abstract

Abstract Regenerative stem cell-based therapies for bronchopulmonary dysplasia (BPD), the most common preterm birth complication, demonstrate promise in animals. Failure to objectively appraise available preclinical data and identify knowledge gaps could jeopardize clinical translation. We performed a systematic review and network meta-analysis (NMA) of preclinical studies testing cell-based therapies in experimental neonatal lung injury. Fifty-three studies assessing 15 different cell-based therapies were identified: 35 studied the effects of mesenchymal stromal cells (MSCs) almost exclusively in hyperoxic rodent models of BPD. Exploratory NMAs, for select outcomes, suggest that MSCs are the most effective therapy. Although a broad range of promising cell-based therapies has been assessed, few head-to-head comparisons and unclear risk of bias exists. Successful clinical translation of cell-based therapies demands robust preclinical experimental design with appropriately blinded, randomized, and statistically powered studies, based on biological plausibility for a given cell product, in standardized models and endpoints with transparent reporting. Significance statement Bronchopulmonary dysplasia (BPD), a chronic lung disease that follows ventilator and oxygen therapy for acute respiratory failure after premature birth, is the most frequent complication of extreme prematurity. BPD is associated with long-term respiratory and neurological consequences reaching into adulthood and currently lacks effective therapy. Regenerative cell-based therapy, demonstrating therapeutic benefit in experimental neonatal lung injury, has now spawned clinical trials. Yet there has been no systematic review to assess the extent of current evidence regarding safety and efficacy of cell-based therapies in preclinical BPD and identify gaps that could jeopardize successful clinical translation.