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

BackgroundMesenchymal 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.MethodsSDF-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.ResultsAdministration 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.ConclusionsThe 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.

• Publication year

  2017

• Venue

  Respiratory Research

• Publication date

  2017-07-12

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1186/s12931-017-0620-zPMID 28701189PMCID 5506612
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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