Prophylactic Administration of Mesenchymal Stromal Cells Does Not Prevent Arrested Lung Development in Extremely Premature-Born Non-Human Primates

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

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.

Details

Original languageEnglish
Pages (from-to)97-111
Number of pages15
JournalStem cells translational medicine
Volume12
Issue number2
Publication statusPublished - 3 Mar 2023
Peer-reviewedYes

External IDs

PubMedCentral PMC9985113
unpaywall 10.1093/stcltm/szac088
WOS 000922740000001
ORCID /0000-0002-8811-8454/work/125191890

Keywords

Research priority areas of TU Dresden

Sustainable Development Goals

Keywords

  • Infant, Newborn, Animals, Humans, Lung, Bronchopulmonary Dysplasia/therapy, Infant, Premature, Primates, Mesenchymal Stem Cells, Cell therapy, Extreme premature birth, Unbiased stereology, Adverse events, Bronchopulmonary dysplasia, Lung development

Library keywords