Article Text

AIRWAY HOMING OF HUMAN AMNIOTIC FLUID STEM CELLS AFTER INTRATRACHEAL ADMINISTRATION IN A RAT MODEL OF BRONCHOPULMONARY DYSPLASIA
  1. D Grisafi1,
  2. A Dedja2,
  3. R Salmaso3,
  4. M Piccoli4,
  5. V Vanzo5,
  6. A Milan5,
  7. R Tomanin1,
  8. A Fassina3,
  9. M Scarpa1,
  10. L Chindetti5,
  11. M Pozzobon4,
  12. P De Coppi4,6,
  13. E Cozzi7,8,
  14. R De Caro9,
  15. A Porzionato9,
  16. V Macchi9,
  17. P Zaramella5
  1. 1Gene Therapy Laboratory and Centre for Rare Diseases, Department of Pediatrics, University of Padova, Padova, Italy
  2. 2Department of Surgical and Gastroenterological Sciences “PG Cevese”, University of Padova, Padova, Italy
  3. 3Section of Pathology, Department of Oncological and Surgical Sciences, University of Padova, Padova, Italy
  4. 4Stem Cell Processing Laboratory, Department of Pediatrics, University of Padova, Padova, Italy
  5. 5Neonatal Intensive Care Unit, Department of Pediatrics, University of Padova, Padova, Italy
  6. 6Surgery Unit, Great Ormond Street Hospital and Institute of Child Health College London, London, UK
  7. 7Padova General Hospital, Padova, Italy
  8. 8CORIT Consorzio Per la Ricerca Sul Trapianto Di Organi, Padova, Italy
  9. 9Department of Anatomy and Physiology, University of Padova, Padova, Italy

Abstract

Objective The aim of this study was to evaluate homing and engraftment of human AFS cells and their distribution after intratracheal administration in a 60% oxygen rat model of bronchopulmonary dysplasia (BPD).

Materials and Methods Wild-type Sprague–Dawley newborn rats (n  =  30) were exposed to hyperoxia with 60% of oxygen (BPD group) from the day of birth to postnatal day 14. Human AFS cells, previously transduced with recombinant adenoviral vectors expressing lacZ and EGFP, at 5 pfu/cell, were administered intratracheally at postnatal day 21, at the amount of 1.5 × 106 cells/animal in a total volume of 70 μl of medium. A BPD placebo received resuspension medium, whereas the group exposed to normoxia served as the control group. At the experimental endpoints all animals were killed and lungs were harvested for morphology and X-gal staining.

Results At 3 weeks posttransplant the BPD rats showed lacZ-positive cells in bronchial sections, at 4 weeks they showed lacZ-positive cells in the alveoli walls (ranging from 1% to 2%). At 3 weeks posttransplant the BPD rats treated with human AFS cells also showed an increased alveoli number and a decreased septal thickening, conditions further improved at 4 weeks posttransplant. Immunohistochemical staining was also performed.

Conclusions We described the administration of human AFS cells in a 60% oxygen rat model of BPD and evaluated homing and histological signs of efficacy of the procedure. A bronchial homing was observed in the third posttransplant week and an alveolar homing was found in the fourth week. Increased alveoli numbers and decreased septal thickening were also detected.

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