Antonia Napoli

University of California, Los Angeles, Los Ángeles, California, United States

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Publications (6)11.78 Total impact

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    ABSTRACT: Rat spinal fusion model. This study aimed to assess the ability of rat bone marrow cells (RBMCs) transfected with bone morphogenetic protein (BMP)-2-containing lentivirus to induce a posterolateral spinal fusion in a rat model. Spinal arthrodesis is a commonly performed spinal procedure and autograft remains the standard for achieving spinal fusion. However, its procurement is associated with significant morbidity, and the rate of pseudoarthrosis has been reported to be 5% to 43%. Nonunion frequently leads to an unsatisfactory resolution of clinical symptoms and usually results in high medical costs and morbidity as well as the need for additional surgeries. These problems have led surgeons to search for alternative solutions to stimulate bone formation. Recombinant BMPs have also been used successfully in clinical trials. However, large doses of BMPs were required to induce adequate bone repair. The development of a regional gene therapy may be a more efficient method to deliver proteins to a specific anatomic site. Furthermore, adeno-BMP-2-producing rat bone marrow-derived cells have been used successfully to induce posterior spinal fusion. Recently, lentiviral vectors on the basis of human immunodeficiency virus have been developed for gene therapy. Lentiviruses are capable of insertion into the host genome, ensuring a prolonged gene expression. However, safety issues are a major concern when adopting these vectors for clinical use. In vitro study, we used RBMCs transfected with lentivirus vectors encoding BMP-2 (Lenti-BMP-2), RBMCs transfected with lentivirus vectors encoding the green fluorescent protein (GFP) (Lenti-GFP), and untransfected RBMCs; the latter 2 were used as controls. Alkaline phosphatase (ALP) staining and ALP activity were compared between the groups to assess the ability of the Lenti-BMP-2-transfected RBMCs to stimulate osteoblastic differentiation. In the rat posterolateral spine fusion model, the experimental study comprised 4 groups. Group 1 comprised 6 animals that were implanted with a collagen sponge containing 5 million RBMCs transfected with Lenti-BMP-2. Group 2 comprised 3 animals that were implanted with a collagen sponge containing 5 million RBMCs transfected with Lenti-GFP. Group 3 comprised 6 animals that were implanted with a collagen sponge containing 5 million untransfected RBMCs. Group 4 comprised 3 animals that were implanted with a collagen sponge alone. The rats were assessed by radiographs obtained at 4, 6, and 8 weeks. After death, their spines were explanted and assessed by manual palpation, high-resolution microcomputerized tomography, and histologic analysis. The ALP staining was significantly greater in the Lenti-BMP-2-transfected RBMCs than in the untransfected RBMCs and the Lenti-GFP-transfected RBMCs. The ALP activity was 3-fold greater in the Lenti-BMP-2-transfected RBMCs than in the untransfected RBMCs and the Lenti-GFP-transfected RBMCs. In the rat spine fusion model, radiographic evaluation, high-resolution microcomputerized tomography, and manual palpation revealed spinal fusion in all the rats in Group 1 at 8 weeks. Groups 2, 3, and 4 comprised the control group. None of the rats in the control group (0 of 12) developed fusion at L4-L5. The present study demonstrated that BMP-2-producing RBMCs, created through lentiviral gene transfer, induced sufficient spinal fusion. The use of lentiviral vectors that contain the cDNA for BMP-2 will be a novel and promising approach for a spinal fusion strategy.
    No preview · Article · Aug 2008 · Journal of Spinal Disorders & Techniques
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    ABSTRACT: A prospective 8-week interventional trial employing a rat model of spinal fusion to test the effect on bone morphogenetic protein binding peptide (BBP) on rhBMP-2 induced bone healing. To determine if the addition of BBP to the collagen sponges used as a carrier for rhBMP-2 reduces the amount of rhBMP-2 required to achieve a satisfactory clinical outcome. Bone morphogenetic proteins (BMPs) although effective in promoting osseous growth and spinal fusion have limitations in their extensive use because of higher costs and possible adverse effects including ectopic bone formation and local inflammatory reaction, particularly in the cervical spine. Posterolateral intertransverse process spinal fusion at L4-L5 was performed in Lewis rats. Two doses of BBP (500 microg, and 1000 microg) were tested with or without "low dose" (1 microg) rhBMP-2 and the results were compared with the low dose (1 microg) rhBMP-2. Fusion was evaluated by radiology, histology, and manual palpation tests. Radiology revealed significant earlier fusion with 1000 microg BBP + 1 microg BMP-2 combination when compared with low dose BMP-2 (1 microg) only (P < 0.05). Manual palpation and histology at eighth week revealed higher rate of fusion with the same combination with a nearly significant difference (P = 0.057). Specific growth factor binding agents, such as BBP, can be compounded into carriers used in fusion procedures to decrease the dosage of BMP and possibly decrease the side effects which are most likely dose-related. This may also decrease costs and improve clinical outcomes.
    No preview · Article · Jul 2008 · Spine

  • No preview · Article · Sep 2007 · The Spine Journal

  • No preview · Article · Sep 2007
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    ABSTRACT: The safety of allograft material has come under scrutiny because of recent reports of allograft-associated bacterial and viral infections in tissue recipients. Gamma irradiation, although being one of the most effective ways of terminal sterilization, has been shown to affect the biomechanical properties of allograft bone. It may also have detrimental effects on the osteoinductivity of allograft material such as demineralized bone matrix (DBM) by the denaturation of proteins because of heat generated by irradiation. Sterilization of DBM material is an important variable in processing graft materials. This is considered to be one of the factors leading to different fusion rates observed with different commercially available DBM products, as the sterilization procedure itself may affect the osteoinductivity of the material. Currently, there is no ideal sterilization technique that limits the detrimental effect on osteoinductivity and fusion rates.
    No preview · Article · Aug 2007 · The Spine Journal
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    ABSTRACT: Recombinant growth factors bone morphogenetic protein-2 (BMP-2) and BMP-7 are currently approved for human use but are associated with various adverse effects including ectopic bone formation and local inflammatory reaction. The development of alternative growth factors may help minimize the adverse effects of current osteoinductive therapeutics. Nell-1 (Nel-like molecule-1; Nel [a protein strongly expressed in neural tissue encoding epidermal growth factor like domain]) is a novel secretory molecule that appears to act more specifically on osteoblasts than the BMPs, which can act on multiple cell types. From a molecular point of view, Nell-1 is directly regulated by runt-related transcription factor 2 (Runx2/Cbfa1), a master regulatory gene controlling bone formation. Previous studies showed that Nell-1 accelerates osteogenic differentiation in vitro and calvarial bone formation in vivo. We hypothesize that Nell-1 may also effectively form bone in spinal fusion.
    No preview · Article · Feb 2007 · The Spine Journal