Large-Scale Bicortical Skull Bone Regeneration Using Ex vivo Replication-Defective Adenoviral-Mediated Bone Morphogenetic Protein—2 Gene—Transferred Bone Marrow Stromal Cells and Composite Biomaterials

2009 ◽  
Vol 65 (suppl_6) ◽  
pp. ons75-ons83 ◽  
Author(s):  
Sophia Chia-Ning Chang ◽  
Tsung-Min Lin ◽  
Hui-Ying Chung ◽  
Philip Kuo-Ting Chen ◽  
Feng-Huei Lin ◽  
...  

Abstract Objective: Bone marrow stromal cells (BMSCs) have great potential in bone repair. We developed an animal model to test the hypothesis that ex vivo gene transfer of human bone morphogenetic protein (BMP)-2 to BMSCs via a replication-defective (E1A-deleted) adenovirus vector (AdV) with appropriate biopolymers would enhance autologous bone formation during repair of a large-scale skull defect. Methods: Eighteen miniature swine were treated with AdV BMP-2-transduced BMSCs in biopolymer (group 1), BMSCs in biopolymer (group 2), or biopolymer alone (group 3). After 6 months, the swine were killed, and the skull repair was examined by gross pictures, histology, 3-dimensional computed tomography, and biomechanical study. Results: Group 1 showed complete solid bone formation after 6 months, and hema-toxylin and eosin staining demonstrated the presence of mature, woven, well-mineralized bone. Computed tomography showed wholesome repair of the skull defect. Statistical analysis demonstrated a significant difference in bone thickness between groups 1 and 2. Biomechanical testing showed a statistically significant difference in the stiffness of new bone formed in group 1 compared with group 2. Conclusion: The Ad5 E1A-deleted AdV may be the optimal starting vector in ex vivo gene therapy for benign skeletal diseases. Additionally, the use of the gelatin/tricalcium phosphate ceramic/glutaraldehyde biopolymer with AdV BMP-2 gene transfer strongly enhances the bony healing of critical-size bicortical craniofacial defects. This method can be used by modifying the delivery of constructs to malunion treatment, in regional osteoporosis therapy, and spinal fusion.

Nanoscale ◽  
2020 ◽  
Vol 12 (13) ◽  
pp. 7284-7300 ◽  
Author(s):  
Xiangfeng Li ◽  
Minjun Liu ◽  
Fuying Chen ◽  
Yuyi Wang ◽  
Menglu Wang ◽  
...  

Biomimicking the nanostructure of natural bone apatite to enhance the bioactivity of hydroxyapatite (HA) biomaterials is an eternal topic in the bone regeneration field.


2013 ◽  
Vol 18 (6) ◽  
pp. 637-646 ◽  
Author(s):  
Kristine Misund ◽  
Katarzyna A. Baranowska ◽  
Toril Holien ◽  
Christoph Rampa ◽  
Dionne C. G. Klein ◽  
...  

The tumor microenvironment can profoundly affect tumor cell survival as well as alter antitumor drug activity. However, conventional anticancer drug screening typically is performed in the absence of stromal cells. Here, we analyzed survival of myeloma cells co-cultured with bone marrow stromal cells (BMSC) using an automated fluorescence microscope platform, ScanR. By staining the cell nuclei with DRAQ5, we could distinguish between BMSC and myeloma cells, based on their staining intensity and nuclear shape. Using the apoptotic marker YO-PRO-1, the effects of drug treatment on the viability of the myeloma cells in the presence of stromal cells could be measured. The method does not require cell staining before incubation with drugs, and less than 5000 cells are required per condition. The method can be used for large-scale screening of anticancer drugs on primary myeloma cells. This study shows the importance of stromal cell support for primary myeloma cell survival in vitro, as half of the cell samples had a marked increase in their viability when cultured in the presence of BMSC. Stromal cell–induced protection against common myeloma drugs is also observed with this method.


2015 ◽  
Vol 6 (1) ◽  
Author(s):  
Rikke K. Andersen ◽  
Walid Zaher ◽  
Kenneth H. Larsen ◽  
Nicholas Ditzel ◽  
Katharina Drews ◽  
...  

2019 ◽  
Vol 12 (2) ◽  

This study was conducted to determine the effect of bone marrow stromal cells (BMSCs) on progesterone level during pregnancy in ewes. Flurogestone Acetate Sponges 40 mg, followed by 400 i.u. Equine chorionic gonadotropin (eCG) were used to synchronize estrus and ovulation. The animals were divided into three equal groups (5 animals for each group). The 1st and 2nd group injected intravenously after eCG injection with 1x108 and 2x108 respectively with BMSCs while the 3rd group was injected with normal saline which serve as a control group. Blood samples were collected during pregnancy, at day 10, 21, 85 from the jugular vein. At day 10, 21 the results showed that there was a significant difference (p≤0.05) in the level of progesterone between treated groups as compared with the control group. While there was no significant difference between different groups at day 85. It was concluded from this study that BMSCs have a beneficial effect in ewe’s reproductive system, by increasing the level of progesterone at early pregnancy.


2017 ◽  
Vol 30 (02) ◽  
pp. 118-124 ◽  
Author(s):  
Aline Macedo ◽  
John Runciman ◽  
Tom Gibson ◽  
Bruno Minto ◽  
Noel Moens

SummaryObjective: To evaluate the torsional properties of the Targon® Vet Nail System (TVS) in small canine femurs and to compare these properties to those of the 2.4 mm LC-DCP® plates.Methods: Thirty-six cadaveric femurs were allocated to three groups (n = 12). In all bones, points just distal to the lesser trochanter and just proximal to the fabellae were marked and a midshaft transverse osteotomy was performed. Group 1: bones were fixed with the 2.5 mm TVS with the bolts applied at the pre-identified marks. Group 2: A TVS system with 25% shorter inter-bolt distance was used. Group 3: A 7-hole 2.4 mm LCDCP® plates were applied. All constructs were tested non-destructively for 10 cycles, followed by an acute torsion to failure.Results: Torque at yield was 0.806 ± 0.183 and 0.805 ± 0.093 Nm for groups 1 and 2 and 1.737 ± 0.461 Nm for group 3. Stiffness was 0.05 ± 0.01, 0.05 ± 0.007, and 0.14 ± 0.015 Nm/° for groups 1 to 3 respectively. Maximal angular displacement under cyclic loading was 16.6° ± 2.5°, 15.6° ± 2.1°, and 7.8° ± 1.06° respectively. There was no significant difference for any of the parameters between groups 1 and 2. Both torque at yield and stiffness were significantly greater between group 3 and groups 1 and 2.Clinical significance: The TVS had approximately half the torsional strength and approximately 1/3 of the stiffness of the 2.4 mm bone plate. Slippage of the locking mechanism was probably the cause of the early failure. The system should be considered as a low-strength and low-stiffness system when compared to bone plates.


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