Dextranomer/hyaluronic Acid copolymer implant for vesicoureteral reflux: role of myofibroblast differentiation.
OBJECTIVE
Dextranomer/hyaluronic acid implantation is associated with a granulomatous inflammatory reaction, replaced by fibrosis. Appearance of myofibroblasts is considered a crucial event in fibrosis, and CD68 positive cells and other factors are implied in their activation. Mast cells are a source of these factors and tryptase can induce fibroblast to express alpha-smooth muscle actin, which is characteristic of myofibroblasts. We evaluated histological changes in refluxing ureters treated with dextranomer/hyaluronic acid and immunolocalized CD68 positive cells, tryptase mast cells and myofibroblasts.


METHODS
We performed histological, histochemical and immunohistochemical analyses in 22 refluxing ureters treated with dextranomer/hyaluronic acid in comparison with 17 refluxing ureters who underwent ureteral reimplantation but did not receive endoscopic bulking agent. We used CD68 antibody for monocytes/macrophages and epithelioid cells, mast cell tryptase mouse antibody for mast cells, and alpha-smooth muscle actin and vimentin antibodies for myofibroblasts. The area of the ureteral lumen in dextranomer/hyaluronic acid treated and untreated ureteral endings was measured.


RESULTS
Sirius red documented a major grade of histological lesions in dextranomer/hyaluronic acid treated refluxing ureters. CD68 and tryptase mast cell staining showed a significant enhancement of positive cells in dextranomer/hyaluronic acid treated refluxing ureters. Immunostaining for alpha-smooth muscle actin and vimentin displayed a myofibroblastic invasion in dextranomer/hyaluronic acid. Measurement of surface in treated refluxing ureters was significantly less than in untreated refluxing ureters.


CONCLUSIONS
Our data documented a recruitment of CD68 and tryptase positive cells, abnormal accumulation of collagenous stroma and successive extracellular matrix remodeling through differentiation of myofibroblasts. Myofibroblasts might provoke tissue contraction, decreasing the ureteral diameter and modifying the ureteral length-to-diameter ratio, preventing urine reflux.
Arena
Salvatore
S
Department of Pediatric Surgery, Unit of Pediatric Surgery, Vittorio Emanuele Hospital, University of Catania, Catania, Italy. arenasal@inwind.it
Fazzari
Carmine
C
Implatini
Alessandra
A
Torre
Santo
S
Villari
Daniela
D
Arena
Francesco
F
Di Benedetto
Vincenzo
V
D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D002454:Cell Differentiation; D003911:Dextrans; D005260:Female; D005347:Fibroblasts; D006801:Humans; D006820:Hyaluronic Acid; D007223:Infant; D008297:Male; D008407:Mast Cells / Q000378:metabolism; D032446:Myoblasts / Q000166:cytology*; D019736:Prostheses and Implants; D012189:Retrospective Studies; D053802:Tryptases / Q000096:biosynthesis; D014513:Ureter / Q000276:immunology* / Q000473:pathology*; D014718:Vesico-Ureteral Reflux / Q000628:therapy*; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D003911:Dextrans; D006820:Hyaluronic Acid; D053802:Tryptases; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C487487:dextranomer-hyaluronic acid copolymer