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Respir Res. 2017 Jul 12;18(1):137. doi: 10.1186/s12931-017-0620-z.

Stromal derived factor-1 mediates the lung regenerative effects of mesenchymal stem cells in a rodent model of bronchopulmonary dysplasia.

Author information

1
Department of Pediatrics, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
2
Department of Pediatrics, University of Miami Miller School of Medicine, Miami, FL, USA.
3
Batchelor Children's Research Institute, University of Miami Miller School of Medicine, Miami, FL, USA.
4
The Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, FL, USA.
5
Department of Medicine/Cardiovascular Division, University of Miami Miller School of Medicine, Miami, FL, USA.
6
Department of Molecular and Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, FL, USA.
7
Department of Pediatrics, University of Miami Miller School of Medicine, Miami, FL, USA. Kyoung3@med.miami.edu.
8
Batchelor Children's Research Institute, University of Miami Miller School of Medicine, Miami, FL, USA. Kyoung3@med.miami.edu.
9
The Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, FL, USA. Kyoung3@med.miami.edu.

Abstract

BACKGROUND:

Mesenchymal stem cells (MSCs) attenuate lung injury in experimental models of bronchopulmonary dysplasia (BPD). Stromal derived factor-1 (SDF-1), a chemokine secreted by MSCs, modulates angiogenesis and stem cell recruitment. Here we tested the hypothesis that SDF-1 mediates MSC protective effects in experimental BPD by modulating angiogenesis.

METHODS:

SDF-1 was knocked down in MSCs using lentiviral vectors carrying anti-SDF-1 short hairpin RNA (MSC-SDF KD). Non-silencing short hairpin RNA was used as control (MSC-NS control). Newborn rats exposed to normoxia or hyperoxia (FiO2 = 0.85) for 3 weeks, were randomly assigned to receive a single intra-tracheal injection (IT) of MSC-NS control or MSC-SDF KD (1 × 106 cells/50 μl) or placebo on postnatal day 7. The degree of alveolarization, lung angiogenesis, inflammation, and pulmonary hypertension (PH) were assessed at postnatal day 21.

RESULTS:

Administration of IT MSC-NS control improved lung alveolarization, angiogenesis and inflammation, and attenuated PH in newborn rats with hyperoxia-induced lung injury (HILI). In contrast, knockdown of SDF-1 in MSCs significantly reduced their beneficial effects on alveolarization, angiogenesis, inflammation and PH.

CONCLUSIONS:

The therapeutic benefits of MSCs in neonatal HILI are in part mediated by SDF-1, through anti-inflammatory and angiogenesis promoting mechanisms. Therapies directly targeting this chemokine may provide a novel strategy for the treatment of BPD.

PMID:
28701189
PMCID:
PMC5506612
DOI:
10.1186/s12931-017-0620-z
[Indexed for MEDLINE]
Free PMC Article

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