Callus formation enhanced by BMP‐7 ex vivo gene therapy during distraction osteogenesis in rats

Abstract

This study was designed to observe the effects of bone morphogenetic protein-7 (BMP-7) ex vivo gene therapy on callus formation during rat mandibular distraction osteogenesis (DO). Fifty-four Sprague-Dawley rats underwent osteodistraction of the right mandible and were then randomly divided into three groups. Immediately after distraction, autologous bone marrow mesenchymal stem cells (MSCs) transfected with BMP-7, MSCs untransfected with BMP-7, and physiological saline were injected into the distraction gaps of the mandibles in groups A, B, and C, respectively. Nine animals from each group were euthanized at 2 and 6 weeks after completion of distraction. The distracted mandibles were removed and processed for radiographic, histological, immunohistochemical, and scanning electron microscopic examinations as well as Ca/P ratio analysis. Group A animals showed greater bone formation and earlier mineralization in the distracted callus when compared with group B. Similarly increased callus formation was found in group B than group C. Positive immunostaining of BMP-7 was observed in the distracted callus in all groups. However, BMP-7 expression was much stronger in group A compared with groups B and C. The results of this study suggest that BMP-7-mediated ex vivo gene transfer based on MSCs may accelerate callus formation in distraction osteogenesis and facilitate consolidation. Local gene therapy may ultimately be an alternative or supplemental approach to DO enhancement, especially for patients whose osteogenic potentials are compromised by diseases such as osteoporosis, severe trauma, and postoncologic irradiation. ß

Genetically Engineered Mesenchymal Stem Cells: The Ongoing Research for Bone Tissue Engineering

“…BMP-7 plays a key role in osteoblast differentiation, and there is only one study in which MSCs are engineered with BMP-7. Engineered MSCs are seeded in the distraction gaps of the mandibles, and the study demonstrates accelerated callus formation in distraction osteogenesis (Hu et al, 2007). BMP-4 is associated with bone and cartilage development and fracture repair.…”

“…Although there are remarkable improvements in its transfect efficiency in recent years, the nonviral vectors remain less efficient in delivery than viral vectors. Although BMP-7 and BMP-2 gene have been successfully engineered into MSCs via liposomes (Park et al, 2003;Hu et al, 2007), further optimization of liposome or other nonviral formulations is still needed.…”

Adipose-derived stem cells transfected with pEGFP-OSX enhance bone formation during distraction osteogenesis

“…The rabbit model has been reported in many previous studies dealing with mandibular distraction (Qi et al, 2006;Hu et al, 2007;Lai et al, 2011). Briefly, the rabbits were given penicillin with at a dose of 15 U/kg prior to operation; anesthesia was achieved by intravenous administration of pentobarbital (1 mg/kg) and subcutaneous injection of local anesthesia [1% (w/v) lidocaine].…”

“…Histological analysis was performed in a prospective, randomized, and blinded manner by two experienced pathologists, similar to the methods of Ashinoff et al (2004) and Hu et al (2007). Three parameters, including the thickness of new trabeculae (TNT; μm), and the volumes of the newly generated cortical bone (NBV1) and the cancellous bone (NBV2) of the distracted regions, were measured in 10 discontinuous slices of each specimen (Ashinoff et al, 2004;Hu et al, 2007). The means of TNT, NBV1, and NBV2 for groups A, B, and C were subjected to statistical analysis.…”

Bone Regeneration Is Promoted by Orally Administered Bovine Lactoferrin in a Rabbit Tibial Distraction Osteogenesis Model

“…Various approaches have been studied to accelerate the process of bone formation and consolidation in distraction osteogenesis including low-intensity pulsed ultrasound [5], systemic use of bisphosphonates [10] and parathyroid hormone [17], local application of various potent bone anabolic agents such as BMPs [22,23], VEGF [25], transforming growth factor-b [29], basic fibroblast growth factor [16], IGF-1 [30], and platelet-rich plasma [20], and local transplantation of bone mesenchymal stem cells [28,31] and gene therapy [12]. However, the effects of these approaches on distraction osteogenesis remain controversial and none of the interventions has proven to be clinically effective.…”