PT  - JOURNAL ARTICLE
AU  - Llontop, Pedro
AU  - Lopez-Fernandez, Daniel
AU  - Clavo, Bernardino
AU  - Afonso Martín, Juan Luis
AU  - Fiuza-Pérez, María D
AU  - García Arranz, Mariano
AU  - Calatayud, Joaquín
AU  - Molins López-Rodó, Laureano
AU  - Alshehri, Khalid
AU  - Ayub, Adil
AU  - Raad, Wissam
AU  - Bhora, Faiz
AU  - Santana-Rodríguez, Norberto
TI  - Airway transplantation of adipose stem cells protects against bleomycin-induced pulmonary fibrosis
AID  - 10.1136/jim-2017-000494
DP  - 2018 Apr 01
TA  - Journal of Investigative Medicine
PG  - 739--746
VI  - 66
IP  - 4
4099  - http://jim.bmj.com/content/66/4/739.short
4100  - http://jim.bmj.com/content/66/4/739.full
SO  - J Investig Med2018 Apr 01; 66
AB  - 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 µL saline (sham), 2.5 UI/kg BLM in 500 µL saline (BLM), and 2×106 ADSC in 100 µL 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, Nfkβ, IL-1, IL-6, Col4, and Tgfβ1 mRNA gene expression were determined using real-time quantitative-PCR. Ashcroft index was: control=0; sham=0.37±0.07; BLM=6.55±0.34 vs 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), Nfkβ (P=0.009), Col4 (P=0.004), Tgfβ1 (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), Nfkβ (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 Nfkβ (P=0.040) and Tgfβ1 (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, Nfkβ, IL-6, Col4, and Tgfβ1. From a translational perspective, this technique could become a new adjuvant treatment for patients with IPF.