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J Investig Med. 2018 Apr;66(4):739-746. doi: 10.1136/jim-2017-000494. Epub 2017 Nov 21.

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

Author information

1
Facultad de Psicología, Universidad Nacional de Educación a Distancia, Madrid, Spain.
2
Instituto Universitario de Investigaciones Biomédicas y Sanitarias (IUIBS)-BioPharm Group, Universidadde Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain.
3
Experimental Surgery Group, Research Unit, Hospital Dr Negrín, Las Palmas de Gran Canaria, Spain.
4
Experimental Surgery and Medicine Unit, Hospital General Gregorio Marañon. Instituto de Investigación Sanitaria Gregorio Marañon, Madrid, Spain.
5
Pathology Service, Complejo Hospitalario Materno Infantil, Las Palmas de Gran Canaria, Spain.
6
Department of Surgery, Laboratorio de Nuevas Tecnologías, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz, Universidad Autónoma de Madrid, Madrid, Spain.
7
Department of Thoracic Surgery, Hospital Clínico San Carlos, Madrid, Spain.
8
Department of Thoracic Surgery, Hospital Clinic, Barcelona, Spain.
9
Department of Thoracic Surgery, Mount Sinai Health System, New York, USA.
10
Section of Thoracic Surgery, Department of Surgery, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.

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 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.

KEYWORDS:

chronic obstructive; genetic; pulmonary disease; stem cells; transcription

PMID:
29167193
DOI:
10.1136/jim-2017-000494

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