LOCAL ADMINISTRATION OF TGFβ1/VEGF165 GENE-TRANSDUCED BONE MESENCHYMAL STEM CELLS FOR ACHILLES ALLOGRAFT REPLACEMENT OF THE ANTERIOR CRUCIATE LIGAMENT IN RABBITS
Graft remodeling following anterior cruciate ligament (ACL) reconstruction requires a long period of recovery before it is capable of withstanding physiological loads.Graft revascularization is extremely important in the remodeling process.Tn ACL reconstruction,the local administration of vascular endothelial growth factor (VEGF) significantly increased revascularization of the graft,but did not significantly affect the mechanical properties of the graft after implantation (Ju et al.,2006;Yoshikawa,et al.,2006).Our previous studies showed that transforming growth factor-pi (TGFpi) could promote improvements in mechanical strength in Achilles tendon regeneration,by regulating collagen type T and type TTT synthesis,cross-link formation,and matrix-remodeling (Hou et al.,2009).The current study aims to investigate whether the co-expression of TGFβ/VEGF165 could beneficially affect the remodeling of ACL grafts.Bone marrow-derived mesenchymal stem cells (BMSCs),transfected with an adenoviral vector encoding TGFpi,VEGF165 or TGFβ/VEGF165,were surgically implanted into experimental ACL grafts,with non-transfected cells as a control.HE and toluidine blue staining,vascular number,and biomechanical features were analyzed at 3,6,12,and 24 weeks after surgery.The results suggest that TGFpi expression,in the TGFβ/VEGF165-transfected BMSCs,could accelerate the remodeling of the reconstructed ligament.The cross-talk between TGFβ And VEGF165 has positive consequences,as TGFβ/VEGF165-transfected BMSCs significantly promoted angiogenesis of the reconstructed ligament at 3,6,12 weeks,with the best mechanical properties being achieved at 24 weeks.Furthermore,co-expression of these genes is more powerful and efficient than single gene therapy.
TGFpi VEGF165 Gene therapy Adenovirus BMSC ACL.
Xuelei Wei Zebin Mao Yu Hou Lin Lin Tao Xue Lianxu Chen Haijun Wang Changlong Yu
Department of Orthopaedic Surgery,Tianjin Hospital,406 South Jiefang Road,Tianjin,China Department of Biochemistry and Molecular Biology,Peking University School of Basic Medical Sciences, Institute of Sports Medicine,Peking University Third Hospital,Beijing,China
国际会议
北京
英文
118-123
2011-10-19(万方平台首次上网日期,不代表论文的发表时间)