Airway transplantation of adipose stem cells protects against bleomycin-induced pulmonary fibrosis

Abstract

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease with poor prognosis. Adipose-derived stem cells (ADSC) have demonstrated regenerative properties in several tissues. The hypothesis of this study was that airway transplantation of ADSC could protect against bleomycin (BLM)-induced pulmonary fibrosis (PF). Fifty-eight lungs from 29 male Sprague-Dawley rats were analyzed. Animals were randomly divided into five groups: a) control (n=3); b) sham (n=6); c) BLM (n=6); d) BLM+ADSC-2d (n=6); and e) BLM+ADSC-14d (n=8). Animals received 500 mu L saline (sham), 2.5 UI/kg BLM in 500 mu L saline (BLM), and 2x10(6)ADSC in 100 mu L saline intratracheally at 2 (BLM+ADSC-2d) and 14 days (BLM+ADSC-14d) after BLM. Animals were sacrificed at 28 days. Blinded Ashcroft score was used to determine pulmonary fibrosis extent on histology. Hsp27, Vegf, Nfk, IL-1, IL-6, Col4, and Tgf1 mRNA gene expression were determined using real-time quantitative-PCR. Ashcroft index was: control=0; sham=0.37 +/- 0.07; BLM=6.55 +/- 0.34vs sham (P=0.006). BLM vs BLM+ADSC-2d=4.63 +/- 0.38 (P=0.005) and BLM+ADSC-14d=3.77 +/- 0.46 (P=0.005). BLM vs sham significantly increased Hsp27 (P=0.018), Nfk (P=0.009), Col4 (P=0.004), Tgf1 (P=0.006) and decreased IL-1 (P=0.006). BLM+ADSC-2d vs BLM significantly decreased Hsp27 (P=0.009) and increased Vegf (P=0.006), Nfk (P=0.009). BLM+ADSC-14d vs BLM significantly decreased Hsp27 (P=0.028), IL-6 (P=0.013), Col4 (P=0.002), and increased Nfk (P=0.040) and Tgf1 (P=0.002). Airway transplantation of ADSC significantly decreased the fibrosis rate in both early and established pulmonary fibrosis, modulating the expression of Hsp27, Vegfa, Nfk, IL-6, Col4, and Tgf1. From a translational perspective, this technique could become a new adjuvant treatment for patients with IPF.