PMID- 22837858
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20120823
LR  - 20211021
IS  - 2045-8940 (Electronic)
IS  - 2045-8932 (Print)
IS  - 2045-8932 (Linking)
VI  - 2
IP  - 2
DP  - 2012 Apr-Jun
TI  - Mesenchymal stem cell-mediated reversal of bronchopulmonary dysplasia and 
      associated pulmonary hypertension.
PG  - 170-81
LID - 10.4103/2045-8932.97603 [doi]
AB  - Clinical trials have failed to demonstrate an effective preventative or 
      therapeutic strategy for bronchopulmonary dysplasia (BPD), a multifactorial 
      chronic lung disease in preterm infants frequently complicated by pulmonary 
      hypertension (PH). Mesenchymal stem cells (MSCs) and their secreted components 
      have been shown to prevent BPD and pulmonary fibrosis in rodent models. We 
      hypothesized that treatment with conditioned media (CM) from cultured mouse bone 
      marrow-derived MSCs could reverse hyperoxia-induced BPD and PH. Newborn mice were 
      exposed to hyperoxia (FiO(2)=0.75) for two weeks, were then treated with one 
      intravenous dose of CM from either MSCs or primary mouse lung fibroblasts (MLFs), 
      and placed in room air for two to four weeks. Histological analysis of lungs 
      harvested at four weeks of age was performed to determine the degree of alveolar 
      injury, blood vessel number, and vascular remodeling. At age six weeks, pulmonary 
      artery pressure (PA acceleration time) and right ventricular hypertrophy (RVH; RV 
      wall thickness) were assessed by echocardiography, and pulmonary function tests 
      were conducted. When compared to MLF-CM, a single dose of MSC-CM-treatment (1) 
      reversed the hyperoxia-induced parenchymal fibrosis and peripheral PA 
      devascularization (pruning), (2) partially reversed alveolar injury, (3) 
      normalized lung function (airway resistance, dynamic lung compliance), (4) fully 
      reversed the moderate PH and RVH, and (5) attenuated peripheral PA 
      muscularization associated with hyperoxia-induced BPD. Reversal of key features 
      of hyperoxia-induced BPD and its long-term adverse effects on lung function can 
      be achieved by a single intravenous dose of MSC-CM, thereby pointing toward a new 
      therapeutic intervention for chronic lung diseases.
FAU - Hansmann, Georg
AU  - Hansmann G
AD  - Department of Pediatrics, Division of Newborn Medicine, Children's Hospital 
      Boston, Harvard Medical School, Boston, Massachusetts, USA.
FAU - Fernandez-Gonzalez, Angeles
AU  - Fernandez-Gonzalez A
FAU - Aslam, Muhammad
AU  - Aslam M
FAU - Vitali, Sally H
AU  - Vitali SH
FAU - Martin, Thomas
AU  - Martin T
FAU - Mitsialis, S Alex
AU  - Mitsialis SA
FAU - Kourembanas, Stella
AU  - Kourembanas S
LA  - eng
GR  - P50 HL067669/HL/NHLBI NIH HHS/United States
GR  - R01 HL055454/HL/NHLBI NIH HHS/United States
GR  - R01 HL085446/HL/NHLBI NIH HHS/United States
GR  - T32 HD007466/HD/NICHD NIH HHS/United States
PT  - Journal Article
PL  - United States
TA  - Pulm Circ
JT  - Pulmonary circulation
JID - 101557243
PMC - PMC3401871
OTO - NOTNLM
OT  - airway hyperresponsiveness
OT  - chronic lung disease of infancy
OT  - hyperoxia
OT  - lung injury
OT  - lung vascular pruning
COIS- Conflict of Interest: None declared.
EDAT- 2012/07/28 06:00
MHDA- 2012/07/28 06:01
PMCR- 2012/04/01
CRDT- 2012/07/28 06:00
PHST- 2012/07/28 06:00 [entrez]
PHST- 2012/07/28 06:00 [pubmed]
PHST- 2012/07/28 06:01 [medline]
PHST- 2012/04/01 00:00 [pmc-release]
AID - PC-2-170 [pii]
AID - 10.4103/2045-8932.97603 [doi]
PST - ppublish
SO  - Pulm Circ. 2012 Apr-Jun;2(2):170-81. doi: 10.4103/2045-8932.97603.