Optimizing a Mesenchymal Stromal Cell Product for Treating Bronchopulmonary Dysplasia

Abstract

Bronchopulmonary dysplasia (BPD) is the most common and severe chronic lung disease affecting premature infants following exposure to hyperoxia and inflammation, with no cure. BPD leads to arrested alveolar growth, pulmonary hypertension (PH) and lifelong breathing difficulties. Mesenchymal stromal cells (MSCs) are multi-potent cells with anti-inflammatory, immunomodulatory and regenerative properties. We previously showed that umbilical cord (UC)-derived MSCs isolated from different donors provide varying lung-protective effects in experimental BPD. Induced pluripotent stem cells (iPSCs) from a single donor have been proposed to provide a large and homogenous pool of iPSC-derived MSCs (iMSCs). Here, we demonstrate that iMSCs improve indicators of PH in a rat neonatal lung injury model. In comparison, we found that only two out of six UC-MSC donors provided therapeutic benefits. Overall, our work demonstrates that iMSCs from a single donor are possible candidates for treating BPD without inter-donor variability, increasing their potential for successful clinical translation.