scholarly journals Basic Fibroblast Growth Factor-Anchored Multilayered Mesenchymal Cell Sheets Accelerate Periosteal Bone Formation

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Kentaro Uchida ◽  
Gen Inoue ◽  
Osamu Matsushita ◽  
Kyosuke Horikawa ◽  
Hiroyuki Sekiguchi ◽  
...  
Keyword(s):  
Growth Factor ◽  
Bone Formation ◽  
Bone Mineral Content ◽  
Fibroblast Growth Factor ◽  
Bone Mineral ◽  
Basic Fibroblast Growth Factor ◽  
Mineral Content ◽  
Graft Material ◽  
Fibroblast Growth ◽  
Callus Volume

Cell-based regenerative therapy has the potential to repair bone injuries or large defects that are recalcitrant to conventional treatment methods, including drugs and surgery. Here, we developed a multilayered cell-based bone formation system using cells coated with fibronectin-gelatin (FN-G) nanofilms. The multilayered mesenchymal cells (MLMCs) were formed after two days of culture and were shown to express higher levels of BMP-2 and VEGF compared to monolayer cultures of MCs. The MLMCs were used as a graft material in combination with a fusion protein consisting of basic fibroblast growth factor (bFGF), polycystic kidney disease (PKD) domain, and the collagen-binding domain (CBD) of Clostridium histolyticum collagenase. In femur sites grafted with the MLMCs, significantly higher levels of callus volume and bone mineral content were observed compared to the sham controls. The callus volume and bone mineral content were further increased in femur sites grafted with bFGF-PKD-CBD/MLMCs. Taken together, these results suggest that bFGF-PKD-CBD/MLMCs, which can be simply and rapidly generated in vitro, have the potential to promote bone repair when grafted into large defect sites.

Stimulation of endosteal bone formation by systemic injections of recombinant basic fibroblast growth factor in rats.

Endocrinology ◽  
1995 ◽  
Vol 136 (3) ◽  
pp. 1276-1284 ◽  
Author(s):  
T Nakamura ◽  
K Hanada ◽  
M Tamura ◽  
T Shibanushi ◽  
H Nigi ◽  
...  
Keyword(s):  
Growth Factor ◽  
Bone Formation ◽  
Fibroblast Growth Factor ◽  
Basic Fibroblast Growth Factor ◽  
Fibroblast Growth ◽  
Stimulation Of

scholarly journals Basic Fibroblast Growth Factor Fused with Tandem Collagen-Binding Domains from Clostridium histolyticum Collagenase ColG Increases Bone Formation

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Hiroyuki Sekiguchi ◽  
Kentaro Uchida ◽  
Osamu Matsushita ◽  
Gen Inoue ◽  
Nozomu Nishi ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Growth Factor ◽  
Bone Formation ◽  
Fusion Protein ◽  
Fibroblast Growth Factor ◽  
Basic Fibroblast Growth Factor ◽  
Callus Formation ◽  
Mesenchymal Cell ◽  
Fibroblast Growth ◽  
Collagen Binding

Basic fibroblast growth factor 2 (bFGF) accelerates bone formation during fracture healing. Because the efficacy of bFGF decreases rapidly following its diffusion from fracture sites, however, repeated dosing is required to ensure a sustained therapeutic effect. We previously developed a fusion protein comprising bFGF, a polycystic kidney disease domain (PKD; s2b), and collagen-binding domain (CBD; s3) sourced from the Clostridium histolyticum class II collagenase, ColH, and reported that the combination of this fusion protein with a collagen-like peptide, poly(Pro-Hyp-Gly)10, induced mesenchymal cell proliferation and callus formation at fracture sites. In addition, C. histolyticum produces class I collagenase (ColG) with tandem CBDs (s3a and s3b) at the C-terminus. We therefore hypothesized that a bFGF fusion protein containing ColG-derived tandem CBDs (s3a and s3b) would show enhanced collagen-binding activity, leading to improved bone formation. Here, we examined the binding affinity of four collagen anchors derived from the two clostridial collagenases to H-Gly-Pro-Arg-Gly-(Pro-Hyp-Gly)12-NH2, a collagenous peptide, by surface plasmon resonance and found that tandem CBDs (s3a-s3b) have the highest affinity for the collagenous peptide. We also constructed four fusion proteins consisting of bFGF and s3 (bFGF-s3), s2b-s3b (bFGF-s2b-s3), s3b (bFGF-s3b), and s3a-s3b (bFGF-s3a-s3b) and compared their biological activities to those of a previous fusion construct (bFGF-s2b-s3) using a cell proliferation assay in vitro and a mouse femoral fracture model in vivo. Among these CB-bFGFs, bFGF-s3a-s3b showed the highest capacity to induce mesenchymal cell proliferation and callus formation in the mice fracture model. The poly(Pro-Hyp-Gly)10/bFGF-s3a-s3b construct may therefore have the potential to promote bone formation in clinical settings.

In VivoStimulation of Endosteal Bone Formation by Basic Fibroblast Growth Factor in Rats

1993 ◽  
Vol 9 (1) ◽  
pp. 73-80 ◽  
Author(s):  
Hiroshi Mayahara ◽  
Takayasu Ito ◽  
Hirofumi Nagai ◽  
Hiroaki Miyajima ◽  
Ryoichi Tsukuda ◽  
...  
Keyword(s):  
Growth Factor ◽  
Bone Formation ◽  
Fibroblast Growth Factor ◽  
Basic Fibroblast Growth Factor ◽  
Fibroblast Growth

scholarly journals Gelatin Sheet Incorporating Basic Fibroblast Growth Factor Enhances Healing of Devascularized Sternum in Diabetic Rats

Circulation ◽  
2001 ◽  
Vol 104 (suppl_1) ◽  
Author(s):  
Atsushi Iwakura ◽  
Yasuhiko Tabata ◽  
Nobushige Tamura ◽  
Kazuhiko Doi ◽  
Kazunobu Nishimura ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Bone Mineral ◽  
Basic Fibroblast Growth Factor ◽  
Median Sternotomy ◽  
Diabetic Rats ◽  
Wound Complications ◽  
Diabetic Patients ◽  
Fibroblast Growth ◽  
Mineral Density

Background Poor healing of the sternum often limits the use of bilateral internal thoracic arteries (BITAs) after coronary bypass surgery in diabetic patients. We have reported that a gelatin sheet that incorporates basic fibroblast growth factor (bFGF) accelerates sternal healing after BITA removal in normal rats. This study evaluated the effects of the above method for sternal healing in diabetic animals. Methods and Results Diabetic Wistar rats with blood glucose levels >400 mg/dL and body-weight loss >20 g were established by a single intravenous injection of streptozotocin (55 mg/kg). After median sternotomy and BITA removal, 16 diabetic rats received either a gelatin sheet that incorporated bFGF (100 μg/sheet) on the posterior table of the sternum (FGF group, n=9) or no gelatin sheet (control, n=7). Peristernal blood flow, as measured by a noncontact laser Doppler 4 weeks after surgery in the FGF group, recovered to the preoperative level (106±10% versus 82±9%, P <0.01), and marked angiogenesis was also observed around the sternum in the FGF group (30.5±3.2 versus 15.8±2.7 vessels/unit area, P <0.01). Deep sternal wound complications developed in 5 control rats but only in 1 rat in the FGF group ( P <0.05). In the FGF group, histological examination showed improved sternal healing (excellent in 6 rats and slow/poor healing in 3). Bone mineral content as assessed by dual-energy x-ray absorptometry was greater in the FGF group (75.9±18.1 versus 48.9±10.7 mg, P <0.05). Bone mineral density of the sternum was similar between the 2 groups. Conclusions A gelatin sheet that incorporates bFGF may offset sternal ischemia and accelerate sternal bone regeneration and healing, even in diabetic patients.

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