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.

Adenovirus-Mediated Expression of BMP-2 and BFGF in Bone Marrow Mesenchymal Stem Cells Combined with Demineralized Bone Matrix For Repair of Femoral Head Osteonecrosis in Beagle Dogs

“…bFGF-modified BMSCs could accelerate healing after anterior cruciate ligament (ACL) reconstruction. Furthermore, previous studies have demonstrated the superiority of using gene transfer to deliver multiple growth factors for treating orthopedic diseases such as osteoarthritis and ACL injuries [34, 35]. Thus, it is reasonable for us to hypothesize that the simultaneous gene transfer of BMP2 and bFGF would synergistically achieve more efficient bone repair than either gene alone.…”

Sequential application of bFGF and BMP‐2 facilitates osteogenic differentiation of human periodontal ligament stem cells

“…Firstly, apply directly to promote endogenous stem cells proliferation and differentiation . Secondly, transfect stem cells with adenoviral vector carrying bFGF or BMP‐2 to defective area to continuously produce the proteins . Thirdly, implant biological materials which loaded the transfected stem cells with the overexpression of bFGF and BMP‐2 genes into bone defect area .…”

Up-Regulation of TGF-β Promotes Tendon-to-Bone Healing after Anterior Cruciate Ligament Reconstruction using Bone Marrow-Derived Mesenchymal Stem Cells through the TGF-β/MAPK Signaling Pathway in a New Zealand White Rabbit Model

“…The key healing process after ACL reconstruction primarily relies on the integration of the graft with the host bone. Unfortunately, slow and incomplete healing of the tendon-to-bone interface can manifest from inappropriate treatment regimens, which results in knee joint instability, movement dysfunction, cartilage damage and intra-articular meniscus and ultimately leads to inferior functional rehabilitation as well as worsening osteoarthritis of the knee [2,3]. Recently, surgical reconstruction coupled with soft tissue autograft or allograft, including the patellar tendon and hamstring tendon, has become the standard treatment for a torn ACL [4,5].…”