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Original research
Airway transplantation of adipose stem cells protects against bleomycin-induced pulmonary fibrosis
  1. Pedro Llontop1,2,3,4,
  2. Daniel Lopez-Fernandez2,3,
  3. Bernardino Clavo2,3,
  4. Juan Luis Afonso Martín5,
  5. María D Fiuza-Pérez2,3,
  6. Mariano García Arranz6,
  7. Joaquín Calatayud7,
  8. Laureano Molins López-Rodó8,
  9. Khalid Alshehri9,
  10. Adil Ayub9,
  11. Wissam Raad9,
  12. Faiz Bhora9,
  13. Norberto Santana-Rodríguez2,9,10
  1. 1Facultad de Psicología, Universidad Nacional de Educación a Distancia, Madrid, Spain
  2. 2Instituto Universitario de Investigaciones Biomédicas y Sanitarias (IUIBS)-BioPharm Group, Universidadde Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain
  3. 3Experimental Surgery Group, Research Unit, Hospital Dr Negrín, Las Palmas de Gran Canaria, Spain
  4. 4Experimental Surgery and Medicine Unit, Hospital General Gregorio Marañon. Instituto de Investigación Sanitaria Gregorio Marañon, Madrid, Spain
  5. 5Pathology Service, Complejo Hospitalario Materno Infantil, Las Palmas de Gran Canaria, Spain
  6. 6Department of Surgery, Laboratorio de Nuevas Tecnologías, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz, Universidad Autónoma de Madrid, Madrid, Spain
  7. 7Department of Thoracic Surgery, Hospital Clínico San Carlos, Madrid, Spain
  8. 8Department of Thoracic Surgery, Hospital Clinic, Barcelona, Spain
  9. 9Department of Thoracic Surgery, Mount Sinai Health System, New York, USA
  10. 10Section of Thoracic Surgery, Department of Surgery, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
  1. Correspondence to Daniel Lopez-Fernandez, Instituto Universitario de Investigaciones Biomédicas y Sanitarias (IUIBS)-BioPharm Group, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, 35017 Las Palmas, Spain; daniel.lopez{at}ulpgc.es

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.

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

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Footnotes

  • Contributors NS-R, PL, DLF, and BC conceived, designed, and oversaw all of the studies, collection of results, interpretation of the data, and writing of the manuscript and were responsible for the primary undertaking, completion, and supervision of all experiments. PL, DLF, and NS-R conducted animal surgeries, stem cell procedures, sample collections, and gene analysis. JLAM and DLF conducted histological studies. MDF-P, MGA, JC, and LMLR assisted in methodological design and statistical analysis. MGA, LMLR, JC, FB, and WR reviewed and critically edited the manuscript.

  • Funding Beca SEPAR EPID Futuro 2013

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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