THE HEALING OF SEGMENTAL BONE DEFECTS, INDUCED BY RECOMBINANT HUMAN BONE MORPHOGENETIC PROTEIN (rhBMP‐2): A RADIOGRAPHIC, HISTOLOGICAL, AND BIOMECHANICAL STUDY IN RATS

Yasko, AW; Jm, Lane; Fellinger, E.; Rosen, Vicki; Wozney, J A; Ea, Wang

doi:10.1111/j.1532-950x.1993.tb00361.x

Cited by 530 publications

(100 citation statements)

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“…[41][42][43][44] In this experiment, bone formation potential of five recombinant BMP adenoviruses was compared using three assays. Although the same batches of recombinant BMP adenoviruses were Bone formation induced by different BMP adenoviruses in athymic nude animals is an important indicator of the osteogenic potential of BMP genes.…”

Section: Discussionmentioning

confidence: 99%

Osteogenic potential of five different recombinant human bone morphogenetic protein adenoviral vectors in the rat

et al. 2003

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one morphogenetic protein (BMP) adenoviral vectors for the induction of osteogenesis are being developed for the treatment of bone pathology. However, it is still unknown which BMP adenoviral vector has the highest potential to stimulate bone formation in vivo. In this study, the osteogenic activities of recombinant human BMP-2, BMP-4, BMP-6, BMP-7, and BMP-9 adenoviruses were compared in vitro, in athymic nude rats, and in Sprague-Dawley rats. In vitro osteogenic activity was assessed by measuring the alkaline phosphatase activity in C2C12 cells transduced by the various BMP vectors. The alkaline phosphatase activity induced by 2 Â 10 5 PFU/well of BMP viral vector was 4890 Â 10 À12 U/well for ADCMVBMP-9, 302 Â 10 À12 U/well for ADCMVBMP-4, 220 Â 10 À12 U/well for ADCMVBMP-6, 45 Â 10 À12 U/well for ADCMVBMP-2, and 0.43 Â 10 À12 U/ well for ADCMVBMP-7. The average volume of new bone induced by 10 7 PFU of BMP vector in athymic nude rats was 0.3770.03 cm 3 for ADCMVBMP-2, 0.8970.07 cm 3 for ADCMVBMP-4, 1.0270.07 cm 3 for ADCMVBMP-6, 0.2470.05 cm 3 for ADCMVBMP-7, and 0.6370.07 cm 3 for ADCMVBMP-9. In immunocompetent Sprague-Dawley rats, no bone formation was demonstrated in the ADCMVBMP-2, ADCMVBMP-4, and ADCMVBMP-7 groups. ADCMVBMP-6 at a viral dose of 10 8 PFU induced 0.1070.03 cm 3 of new bone, whereas ADCMVBMP-9 at a lower viral dose of 10 7 PFU induced more bone, with an average volume of 0.2970.01 cm 3 .

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Section: Discussionmentioning

confidence: 99%

Osteogenic potential of five different recombinant human bone morphogenetic protein adenoviral vectors in the rat

et al. 2003

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“…A rat femoral segmental defect model was used in this study [23,47,48]. Inbred Fischer 344 (RTI") and Brown Norway (RTI") rats (both from Charles River, Wilmington, MA) were used as donors or recipients.…”

Section: Eyperiinental D E S I Pmentioning

confidence: 99%

“…A rat femoral segmental defect model [23,47,48] was used in this study. A bone defect was surgically created on rat right femurs.…”

Section: Preparufion Of Bmp-2 Cwgineercd M S Cmentioning

confidence: 99%

“…IL) for a 3 0 5 exposure at 25 kV and 3 mA. Radiography of the amount of bone tissue formation in the femoral defect sites was scored on a 6-point scale [23,47,48]. with 0 points indicating no bone formation: 1 point, bone filling less than 25% of the defect; 2 points, hone filling 25-50"/;>; 3 points, bone filling 51-75%; 4 points, bone filling 76-99'%1: and 5 points, bone filling 1 0O' !h of the defect.…”

Section: Rtrdiogrtrphic Ruarninutionmentioning

confidence: 99%

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Engineered allogeneic mesenchymal stem cells repair femoral segmental defect in rats

Tsuchida

Hashimoto

Crawford

et al. 2003

Journal Orthopaedic Research

179

121

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Bone marrow derived mesenchymal stem cells (MSC) have been shown to be progenitor cells for mesenchymal tissues. These cells may also provide a potential therapy for bone repair. Our previous studies showed that MSC engineered with the gene for bone morphogenetic protein 2 (BMP-2), a growth factor for bone cells, were capable of differentiating into osteoblast lineage and inducing autologous bone formation in several animal models. Culturing individual MSC for autologous implantation, however, remains problematic. The number of human MSC with osteogenic potential decreases with age, and, in certain diseases, the patient's marrow may be damaged or the healthy cells reduced in number. In this study, we used rats with a femoral segmental defect to investigate whether allogeneic BMP-2 engineered MSC would facilitate bone healing. We show that BMP-2 engineered allogeneic MSC can repair critical bone defects to the same degree as rats treated with BMP-2 engineered autologous MSC, if the allogeneic group receives short-term treatment with immunosuppressant FK506. We also show that allogeneic gene transferred MSC are directly involved in bone repair, in addition to acting as gene deliverers.

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“…BMP7 is one of the main sources of BMPs in limb development (Robert, 2007). In regeneration of damaged bones, BMPs have been known to be important for connecting bones (Yasko and Lane, 1992).…”

Section: Introductionmentioning

confidence: 99%

Bone pattern formation in mouse limbs after amputation at the forearm level

Ide

2012

Developmental Dynamics

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Background: Although urodela amphibians completely regenerate amputated limbs, the potency of limb regeneration in mammalians is very low. In mice and humans, a digit tip regenerates, but no regeneration beyond the digit joint occurs. In this article, we describe the induction of bone formation by BMPs in the forearm, a more proximal region, of neonatal mice. Distal halves of the radius and ulna were removed from limbs amputated at the wrist level in advance, and gelatin rods containing BMPs were grafted in the space of the forearm. BMP-7 and BMP-2 were effective. Results: The induction of bone formation depended on the amount of BMP-7 in grafted gelatin gels. BMP-7 at over 320 ng/limb induced long bones within 10 days. Cartilage formation was always observed before the bone formation as in the case of normal limb development. The origin of cells responsive to BMP-7 is not clear, but the formation of large bone tissues in a relatively short time suggests a wide distribution of precursor cells in the limbs. Grafting of dye-stained mesenchymal tissue fragments suggested that mesenchymal tissues other than the dermis, bone, and joint cartilage are responsive to BMP-7 and form cartilage/bone. Two long bones induced were arranged in parallel fashion in many cases like the radius and ulna. An agonist of hedgehog promoted the formation of bones in the presence of BMP-7. Furthermore, bone elements were fused to stump bones to form a single bone. Conclusions: The results suggest the potency of bone pattern regeneration in the amputated forearm of a neonatal mouse. Developmental Dynamics 241:435-441,

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THE HEALING OF SEGMENTAL BONE DEFECTS, INDUCED BY RECOMBINANT HUMAN BONE MORPHOGENETIC PROTEIN (rhBMP‐2): A RADIOGRAPHIC, HISTOLOGICAL, AND BIOMECHANICAL STUDY IN RATS

Cited by 530 publications

References 0 publications

Osteogenic potential of five different recombinant human bone morphogenetic protein adenoviral vectors in the rat

Osteogenic potential of five different recombinant human bone morphogenetic protein adenoviral vectors in the rat

Engineered allogeneic mesenchymal stem cells repair femoral segmental defect in rats

Bone pattern formation in mouse limbs after amputation at the forearm level

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