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Prophylactic Administration of Mesenchymal Stromal Cells Does Not Prevent Arrested Lung Development in Extremely
Marius A Möbius1,2,3,4, Steven R Seidner4, Donald C McCurnin4
1Neonatology and Pediatric Critical Care Medicine, Department of Pediatrics, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Saxony, Germany.
Insights
Mesenchymal stromal cells (MSC) did not improve lung development in extremely premature baboons. This contrasts with rodent studies, suggesting new approaches are needed for treating premature lung disease.
Area of Science:
- Neonatal Medicine
- Regenerative Medicine
- Pulmonology
Background:
- Premature birth causes significant infant morbidity and mortality.
- Bronchopulmonary dysplasia (BPD) is a common complication of premature birth, characterized by arrested lung development.
- Mesenchymal stromal cell (MSC) therapy shows promise in rodent models of BPD but its efficacy in premature infants is unknown.
Purpose of the Study:
- To evaluate the safety and efficacy of human umbilical cord tissue-derived MSCs in extremely premature non-human primates.
- To determine if MSC therapy can improve lung structure and function in a model of prematurity.
Main Methods:
- Thirteen baboons born at the limit of viability received a single intravenous dose of MSCs or placebo post-birth.
- Animals underwent two weeks of neonatal intensive care, including mechanical ventilation.
- Lung function, cardiovascular stability, and lung tissue structure were assessed using stereology and echocardiography.
Main Results:
- MSC administration was safe and feasible when infused over 15 minutes, but faster infusion was linked to adverse events.
- MSC therapy improved cardiovascular stability but did not improve lung structure or function.
- No signs of MSC engraftment were observed.
Conclusions:
- A single intravenous MSC dose showed no short- to mid-term lung protection in extremely premature baboons.
- Findings contrast with positive results in term-born rodent models of lung development arrest.
- Further research is needed to understand MSC therapy mechanisms for prematurity-related lung diseases.
Abstract:
Premature birth is a leading cause of childhood morbidity and mortality and often followed by an arrest of postnatal lung development called bronchopulmonary dysplasia. Therapies using exogenous mesenchymal stromal cells (MSC) have proven highly efficacious in term-born rodent models of this disease, but effects of MSC in actual premature-born lungs are largely unknown. Here, we investigated thirteen non-human primates (baboons; Papio spp.) that were born at the limit of viability and given a single, intravenous dose of ten million human umbilical cord tissue-derived MSC per kilogram or placebo immediately after birth. Following two weeks of human-equivalent neonatal intensive care including mechanical ventilation, lung function testing and echocardiographic studies, lung tissues were analyzed using unbiased stereology. We noted that therapy with MSC was feasible, safe and without signs of engraftment when administered as controlled infusion over 15 minutes, but linked to adverse events when given faster. Administration of cells was associated with improved cardiovascular stability, but neither benefited lung structure, nor lung function after two weeks of extrauterine life. We concluded that a single, intravenous administration of MSC had no short- to mid-term lung-protective effects in extremely premature-born baboons, sharply contrasting data from term-born rodent models of arrested postnatal lung development and urging for investigations on the mechanisms of cell-based therapies for diseases of prematurity in actual premature organisms.
