Abstract
Radiation-induced pulmonary fibrosis is a common disease and has a poor prognosis owing to the progressive breakdown of gas exchange regions in the lung. Recently, a novel strategy of administering mesenchymal stem cells for pulmonary fibrosis has achieved high therapeutic efficacy. In the present study, we attempted to use human adipose tissue-derived mesenchymal stem cells to prevent disease in Sprague-Dawley rats that received semi-thoracic irradiation (15 Gy). To investigate the specific roles of mesenchymal stem cells in ameliorating radiation-induced pulmonary fibrosis, we treated control groups of irradiated rats with human skin fibroblasts or phosphate-buffered saline. After mesenchymal stem cells were infused, host secretions of hepatocyte growth factor (HGF) and prostaglandin E2 (PGE2) were elevated compared with those of the controls. In contrast, tumour necrosis factor-alpha (TNF-α) and transforming growth factor-beta1 (TGF-β1) levels were decreased after infusion of mesenchymal stem cells. Consequently, the architecture of the irradiated lungs was preserved without marked activation of fibroblasts or collagen deposition within the injured sites. Moreover, mesenchymal stem cells were able to prevent the irradiated type II alveolar epithelial cells from undergoing epithelial-mesenchymal transition. Collectively, these data confirmed that mesenchymal stem cells have the potential to limit pulmonary fibrosis after exposure to ionising irradiation.
Highlights
The anti-fibrotic effects of mesenchymal stem cells on irradiated lungs via stimulating endogenous secretion of hepatocyte growth factor (HGF) and prostaglandin E2 (PGE2)
It is essential to first explain the pathogenesis of Radiationinduced pulmonary fibrosis (RIPF) before analysing the exact roles played by Ad-Mesenchymal stem cells (MSCs) in protecting lungs against radiation-induced fibrosis
Apart from the ionising irradiation contributing to the development of pulmonary fibrosis by directly activating epithelialmesenchymal transition (EMT) in type II alveolar epithelial cells (AECs), fibrotic formation is largely driven by the abnormal release of fibrosis facilitators, such as TGF-b, CTGF, tumour necrosis factor-alpha (TNF-a), IFN-c, IL-1b, and IL-6, after exposure to high doses of ionising radiation[3,25,27]
Summary
The anti-fibrotic effects of mesenchymal stem cells on irradiated lungs via stimulating endogenous secretion of HGF and PGE2. We attempted to use human adipose tissue-derived mesenchymal stem cells to prevent disease in Sprague-Dawley rats that received semi-thoracic irradiation (15 Gy). Gene therapy was used to treat RIPF by using bone marrow-derived MSCs as carriers of the genes for hepatocyte growth factor (HGF) or TGF-b type II receptor[9,10] These genetically modified MSCs travel to injured sites and inhibit the TGF-b/Smad signalling pathway by releasing large amounts of HGF; this inhibition results in increased expression of Smad[7], which interferes with the phosphorylation of Smad2/3. In the present study, we aimed to evaluate whether Ad-MSCs have anti-fibrotic potential by examining the effects of introducing Ad-MSCs from healthy human donors into a Sprague-Dawley rat model of RIPF
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call