Human amniotic fluid stem cells protect rat lungs exposed to moderate hyperoxia

Abstract

Background: Treatment of bronchopulmonary dysplasia (BPD) remains as yet an unmet clinical need and recently stem cells have been proposed as a therapeutic tool in animal models. We investigated the role of amniotic fluid stem cells (AFS) in an adult rat model of hyperoxia lung injury.

Methods: Fifty Sprague-Dawley rats were, at birth, randomly exposed to moderate hyperoxia or room air for 14 days and a single dose of human amniotic fluid stem (hAFS) or human Fibroblasts (hF), cells was delivered intratracheally (P21). At P42 animals were euthanized and lung tissue examined using histology, immunohistochemistry, PCR, and ELISA. hAFS cells characterization and homing were studied by immunofluorescence.

Results: In rats treated with hAFS and hF cells 16S human rRNA fragment was detected. Despite a low level of pulmonary hAFS cell retention (1.43 ± 0.2% anti-human-mitochondria-positive cells), the lungs of the treated animals revealed higher secondary crest numbers and lower mean linear intercept and alveolar size, than those exposed to hyperoxia, those left untreated or treated with hF cells. Except for those treated with hAFS cells, moderate hyperoxia induced an increase in protein content of IL-6, IL-1β, as well as IF-γ and TGF-1β in lung tissues. High VEGF expression and arrangement of capillary architecture in hAFS cell group were also detected.

Conclusions: Treatment with hAFS cells has a reparative potential through active involvement of cells in alveolarization and angiogenesis. A downstream paracrine action was also taken into account, in order to understand the immunodulatory response.

Keywords: hAFS cells; hyperoxia; lung repair; transplantation.