title: Enhancement of tendon-to-bone healing after anterior cruciate ligament reconstruction using bone marrow-derived mesenchymal stem cells genetically modified with bFGF/BMP2.
abstract: Many strategies, including various growth factors and gene transfer, have been used to augment healing after anterior cruciate ligament (ACL) reconstruction. The biological environment regulated by the growth factors during the stage of tendon-bone healing was considered important in controlling the integrating process. The purpose of this study was to evaluate the effects of bone marrow-derived mesenchymal stem cells (BMSCs) genetically modified with bone morphogenetic protein 2 (BMP2) and basic fibroblast growth factor (bFGF) on healing after ACL reconstruction. BMSCs were infected with an adenoviral vector encoding BMP2 (AdBMP2) or bFGF (AdbFGF). Then, the infected BMSCs were surgically implanted into the tendon-bone interface. At 12 weeks postoperatively, the formation of abundant cartilage-like cells, smaller tibial bone tunnel and significantly higher ultimate load and stiffness levels, through histological analysis, micro-computed tomography and biomechanical testing, were observed. In addition, the AdBMP2-plus-AdbFGF group had the smallest bone tunnel and the best mechanical properties among all the groups. The addition of BMP2 or bFGF by gene transfer resulted in better cellularity, new bone formation and higher mechanical property, which contributed to the healing process after ACL reconstruction. Furthermore, the co-application of these two genes was more powerful and efficient than either single gene therapy.
authors.affiliation: Department of Orthopaedic Surgery, Zhongnan Hospital, Wuhan University, Wuhan, China.
authors.forename: Biao
authors.initials: B
authors.lastname: Chen
authors.affiliation: Department of Orthopaedic Surgery, Zhongnan Hospital, Wuhan University, Wuhan, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Orthopaedic Surgery, Zhongnan Hospital, Wuhan University, Wuhan, China.
authors.forename: Yong-Jian
authors.initials: YJ
authors.lastname: Qi
authors.affiliation: Department of Orthopaedic Surgery, Zhongnan Hospital, Wuhan University, Wuhan, China.
authors.forename: Qu-Bo
authors.initials: QB
authors.lastname: Ni
authors.affiliation: Department of Orthopaedic Surgery, Zhongnan Hospital, Wuhan University, Wuhan, China.
authors.forename: Zheng-Qi
authors.initials: ZQ
authors.lastname: Pan
authors.affiliation: Department of Pharmacology, Basic Medical School, Wuhan University, Wuhan, China.|Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Orthopaedic Surgery, Zhongnan Hospital, Wuhan University, Wuhan, China.|Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, China.
authors.forename: Liao-Bin
authors.initials: LB
authors.lastname: Chen
mesh_terms: D000818:Animals; D059549:Anterior Cruciate Ligament Reconstruction / Q000379:methods*; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics / Q000378:metabolism*; D002470:Cell Survival; D002478:Cells, Cultured; D003131:Combined Modality Therapy; D000229:Dependovirus / Q000235:genetics; D004195:Disease Models, Animal; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism*; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D011817:Rabbits; D014162:Transfection; D016896:Treatment Outcome; D014945:Wound Healing
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D016222:Fibroblast Growth Factor 2