Delivery of basic fibroblast growth factor gene to healing tendon by adeno-associated virus 2 vector and tissue reactions of adeno-associated virus vectors

Abstract

Objective To explore the effect of basic fibroblast growth factor (bFGF) gene transferred by adeno-associated virus (AAV) 2 vectors on tendon healing and to observe tissue reactions of adenovirus, AAV and liposome-plasmid vectors in tendons, Methods Twenty-six flexor digitorum profundus (FDP) tendons from bilateral long toes of 13 chickens were randomly divided into equal 2 groups. Tendons in the experimental group were cut completely and treated with AAV2-bFGF before repair by the modified Kessler method. Tendons as controls were not treated with AAV2-bFGF. Immunohistochemical staining was carried out at 4 weeks and digital tlexion was tested 8 weeks alter surgery. In addition, 36 FDP tendons from 6 rabbits were divided into 3 even groups and injected respectively with adenoviral vector, AAV-luciferase vector, and pCMV-β with liposome vector. At 3, 7, and 14 days, the tendons were harvested and stained with hematoxylin and eosin. Results The AAV2-bFGF treatment remarkably increased the expression of bFGF 4 weeks after surgery, but did not increase resistance to digital flexion. The liposome-plasmid vector resulted in the most prominent tissue reactions in tendons among the 3 vectors tested. The adenoviral vector elicited a moderate degree of tissue reactions. The AAV2 vector caused remarkable reactions in epitenon but almost no reactions in endotenon. Conclusions AAV2-bFGF treatment increases the amount of bFGF in the healing tendons. Adenoviral and AAV vectors elicit less severe tissue reactions than liposome-plasmid. Since the AAV2 vector causes almost no reactions in endotenon, it may be a suitable gene delivery system for future gene transfer to the tendon in vivo. Key words: Tendons; Gene therapy; Fibroblast growth factor 2; Adenovirus; Vectors