THE HORSE AS A LARGE ANIMAL MODEL FOR EXTRA-FETAL DERIVED CELL THERAPY OF CHRONIC RESPIRATORY DISEASES

Abstract

The airway epithelium is subjected to a lifetime exposure to inhaled particles and pathogens that may lead to the development of a variety of infectious and inflammatory respiratory diseases such as chronic bronchitis, asthma and chronic obstructive pulmonary disease. These disorders are typically associated with changes in the architecture of the airway walls,that range from epithelial structure remodeling to complete denudation of the basement membrane. The repair of injuries and the regeneration of the epithelial structure involve stem and progenitor cells. Although both secretory and basal cells are able to proliferate, only basal cells are recently suggested to represent the stem cell (SC) niche of the airway epithelium in human tracheas and bronchi, but the adult secretory cells lose their regeneration potential compared to the fetal secretory cells. For this reason, researchers are considering other sources for exogenous pluripotent SCs for airway tissue engineering. At present, autologous bone marrow and adipose derived MSCs seem to present the most popular SC type used in laryngotracheal tissue engineering. Extra-fetal derived SCs could represent new alternative cell sources for lung regeneration. Investigations of stem cell therapy for murine lung injuries revealed an excellent regeneration potential of extra-fetal derived cells that integrated into the lung and differentiated into pulmonary lineages after injury. Recurrent airway obstruction disease (RAO) in the horse is one of the only naturally occurring diseases in animals that is comparable to bronchial asthma in humans. The anamnestic and reversible nature of equine RAO is similar to some forms of human asthma suggesting a common immunological basis. Based on similarities between human asthma and equine RAO, we propose to use spontaneously RAO affected horses as an animal model in biomedical research. We describe the isolation, in vitro proliferation capacity and labeling of equine extra-fetal derived cells, and preliminary in vivo results indicating that after local injection, labeled cells could be retrieved by bronchoalveolar lavage from selected pulmonary areas.