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Updated: Sep 26, 2025
Intratracheal Instillation of Stem Cells in Term Neonatal Rats
Published on: May 4, 2020
Human bone marrow-derived mesenchymal stem cells rescue neonatal CPAP-induced airway hyperreactivity
P M MacFarlane1, C A Mayer1, A I Caplan2
1Department of Pediatrics, Rainbow Babies & Children's Hospital, Case Western Reserve University, Cleveland, OH 44106, USA.
Insights
Continuous positive airway pressure (CPAP) in preterm infants may cause airway hyperreactivity. Human mesenchymal stem cell (hMSC) therapy shows promise in reversing this CPAP-induced airway hyperreactivity in a mouse model.
Area of Science:
- Neonatal respiratory support
- Stem cell therapy
- Pulmonary physiology
Background:
- Continuous positive airway pressure (CPAP) is vital for preterm infants but may cause airway hyperreactivity (AHR).
- Mesenchymal stem cells (MSCs) show therapeutic potential in various conditions, with ongoing trials for prematurity and bronchopulmonary dysplasia (BPD).
Purpose of the Study:
- To investigate if conditioned medium from human bone-marrow derived mesenchymal stem cells (hMSC) can reverse CPAP-induced AHR in a mouse model.
- To assess the potential of hMSC therapy to mitigate long-term adverse effects of neonatal CPAP on airway function.
Main Methods:
- Neonatal mice received daily CPAP for 7 days.
- At postnatal day 21, precision-cut lung slices were incubated with hMSC-conditioned medium.
- Airway hyperreactivity was measured using methacholine challenge.
Main Results:
- CPAP exposure induced significant AHR compared to controls.
- hMSC-conditioned medium from all three donors completely reversed the CPAP-induced AHR.
- These findings suggest hMSC therapy can counteract CPAP's detrimental effects on airway function.
Conclusions:
- Neonatal CPAP can lead to long-term airway hyperreactivity in former preterm infants.
- hMSC-conditioned medium demonstrates a potent ability to reverse CPAP-induced AHR.
- hMSC therapy represents a potential therapeutic strategy to mitigate adverse pulmonary outcomes in infants treated with CPAP.
Abstract:
Continuous positive airway pressure (CPAP) is a primary non-invasive mode of respiratory support for preterm infants. However, emerging evidence suggests CPAP could be an underlying contributor to the unintended pathophysiology of wheezing and associated airway hyperreactivity (AHR) in former preterm infants. The therapeutic benefits of mesenchymal stem cells (MSCs) have been demonstrated in a variety of animal models and several clinical trials are currently underway to assess their safety profiles in the setting of prematurity and bronchopulmonary dysplasia (BPD). In the present study, using a mouse model of neonatal CPAP, we investigated whether conditioned medium harvested from cultures of human bone-marrow derived mesenchymal stem cells (hMSC) could rescue the CPAP-induced AHR, based upon previous observations of their anti-AHR properties. Newborn mice (male and female) were fitted with a custom-made mask for delivery of daily CPAP 3 h/day for the first 7 postnatal days. At postnatal day 21 (two weeks after CPAP ended), lungs were removed, precision-cut lung slices were sectioned and incubated for 48 h in vitro in conditioned medium collected from cultures of three different hMSC donors. As expected, CPAP resulted in AHR to methacholine compared to untreated control mice. hMSC conditioned medium from the cultures of all three donors completely reversed AHR. These data reveal potential therapeutic benefits of hMSC therapy, which may be capable of rescuing the long-term adverse effects of neonatal CPAP on human airway function.
