Table 4.

Typical cell sources used for epithelialisation.

Organ	Cell type	Advantages	Disadvantages	References
Trachea	Endogenous adult stem cells: Located in basal layers of airways Near pulmonary neuroendocrine cell rests Bronchioalveolar junction Alveolar epithelial surface	Used endogenously for lung repair and regeneration as seen on alveolar surface injuries, no immunogenic response as host cells	Ageing of lungs arises with decreasing repair capacity due to endogenous stem cell failure with age. These cells have been discussed in rodent models but not fully established and have been recently discovered in humans	Chistiakov95
Trachea	ESCs	Very pluripotent and can differentiate to a variety of cell lineages	Ethical problems with procurement. Immunogenicity problem may require immune suppression to prevent host response to graft	Roomans96
Trachea; small intestine	BM-MSCs	Evidence showing epithelium derived from BM-MSCs in mice models (86). Capacity to differentiate into cells outside their lineage (87)	No direct conclusive evidence to show differentiation to epithelium. Controversial, as some believe intraepithelial lymphocytes may be interpreted as donor-derived epithelial cells rather than there being actual epithelial lineage (88).	Gomperts et al.97,98, MacPherson et al.99
Trachea	Adipocyte mesenchymal stem cells	Differentiation to epithelial cells seen in rat models	Immunogenicity problem, may require immune suppression to prevent host response to graft	Suzuki et al.51
Trachea	Amniotic fluid stem cells/amniotic fluid progenitor cells	Wide range of pluripotency of a variety of embryonic germ-layer origins, less tumour inducing than ESCs	Immunogenicity problem, may require immune suppression to prevent host response to graft	Chistiakov95
Trachea	hiPS	Less ethical concern surrounding production and usage and ESC-like pluripotency	Not used in airway tissue engineering and may take time to programme genes to produce hiPS from somatic cell	Chistiakov95
Trachea	Skin epithelial cells	Easy to access and use, show transdifferentiation to airway cells sustained for several months	Inflammation and degrees of stenosis seen post-surgery. Only done in canine models	Kim et al.100
Oesophagus	Squamous epithelial cells	Epithelial cells formed layered structures mimicking native oesophagus. Cytokeratin and alpha-actin staining showed differentiation of transplanted primary epithelial cells	Cells were co-cultured with myoblast cells, so may be confounding factor and co-culturing products enhancing cell differentiation. Cell source was aborted foetus which is difficult to use clinically for multiple reasons	Cen et al.101
Oesophagus	Oral mucosal tissue	Full epithelialisation occurred on the specific area epithelial sheets transplanted, as well as spreading past this area	One case had large oesophageal ulceration, stricture and dysphagia	Ohki et al.102
Bladder	Oral mucosal tissue	Cell sheets contained both progenitor and proliferative cell populations	Exposure to urine affected the viability of the cells and their expression of epithelial cell markers. Lack of elasticity as seen in native bladder. Contraction due to inflammation of bladder wall occurs	Watanabe et al.103
Urethra	Oral cells (seeded as composite model of epithelial oral mucosal cell sheet and muscle cells on collagen scaffold)	Reduced stricture, lumen lined by stratified epithelial cell layer	Positive result may be due to co-culture with muscle cells, growth on collagen scaffold and the support this provided for angiogenesis	Mikami et al.57
Urethra	Bladder urothelial cells	Transitional epithelium as normally found in urethra is seen. Four out of six boys demonstrated urothelium for 8 years	Only four out of six boys eventually grew urothelium and the urothelium was not always present in biopsies taken. Difficult to harvest and culture in vitro	Fossum et al.5
Urethra	Simple squamous mesothelium epithelium	No stricture formation when presented with intervention. Multilayered structure forms with differentiation to urothelium from mesothelium	Epithelium grown on graft was more irregular and contained fewer layers. Smooth muscle formed irregularly underneath and mainly at points of anastomosis. Takes 6 months for full epithelialisation	Gu et al.35

ESC: embryonic stem cell; BM-MSC: bone marrow–mesenchymal stem cell; hiPS: human-induced pluripotent stem cell.