Short-term, long-term and paracrine effect of human umbilical cord-derived stem cells in lung injury prevention and repair in experimental bronchopulmonary dysplasia
- Maria Pierro1,2,
- Lavinia Ionescu1,
- Tiziana Montemurro3,
- Arul Vadivel1,
- Gaia Weissmann2,
- Gavin Oudit4,
- Derek Emery5,
- Sreedhar Bodiga4,
- Farah Eaton1,
- Bruno Péault6,
- Fabio Mosca2,
- Lorenza Lazzari3,
- Bernard Thébaud7
- 1Department of Pediatrics, Cardiovascular Research Center and Pulmonary Research Group, School of Human Development, Women and Children's Health Research Institute, University of Alberta, Edmonton, Canada
- 2Department of Maternal and Pediatric Sciences, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy
- 3Cell Factory, Department of Regenerative Medicine, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
- 4Division of Cardiology, Department of Medicine, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Canada
- 5Department of Radiology and Diagnostic Imaging, University of Alberta, Edmonton, Canada
- 6Department of Orthopedic Surgery, Cellular and Molecular Pathology, David Geffen School of Medicine at UCLA, Los Angeles, California, USA
- 7Department of Pediatrics, Children's Hospital of Eastern Ontario, Ottawa Hospital Research Institute, Sprott Center for Stem Cell Research, University of Ottawa, Department of Cellular and Molecular Medicine, Ottawa, Canada
- Correspondence to Dr Bernard Thébaud, Sprott Centre for Stem Cell Research, Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, ON, Canada K1H 8L6; bthebaud@ohri
- Received 21 June 2012
- Revised 28 September 2012
- Accepted 1 November 2012
- Published Online First 4 December 2012
Background Bronchopulmonary dysplasia (BPD) remains a main complication of extreme prematurity and currently lacks efficient treatment. Rat bone marrow-derived mesenchymal stem cells (MSC) prevent lung injury in an oxygen-induced model of BPD. Human cord is an advantageous source of stem cells that is especially appealing for the treatment of neonatal diseases. The therapeutic benefit after established lung injury and long-term safety of cord-derived stem cells is unknown.
Methods Human cord-derived perivascular cells (PCs) or cord blood-derived MSCs were delivered prophylactically or after established alveolar injury into the airways of newborn rats exposed to hyperoxia, a well-established BPD model.
Results Rat pups exposed to hyperoxia showed the characteristic arrest in alveolar growth with air space enlargement and loss of lung capillaries. PCs and MSCs partially prevented and rescued lung function and structure. Despite therapeutic benefit, cell engraftment was low, suggesting that PCs and MSCs act via a paracrine effect. Accordingly, cell free-derived conditioned media from PCs and MSCs also exerted therapeutic benefit when used either prophylactically or therapeutically. Finally, long-term (6 months) assessment of stem cell or conditioned media therapy showed no adverse lung effects of either strategy, with persistent improvement in exercise capacity and lung structure.
Conclusions Human umbilical cord-derived PCs and MSCs exert short- and long-term therapeutic benefit without adverse lung effects in this experimental model and offer new therapeutic options for lung diseases characterised by alveolar damage.