In Vitro Osteogenic Response of Rat Bone Marrow Cells to bFGF and BMP-2 Treatments

Varkey, Mathew; Kucharski, Cezary; Haque, Takrima; Sebald, Walter; Uludağ, Hasan

doi:10.1097/01.blo.0000200236.84189.87

Cited by 58 publications

(45 citation statements)

References 35 publications

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“…The addition of bFGF to dentin pulp cultures suppressed the increases in ALPase activity, SPARC synthesis, and their mRNA levels [45]. However, other studies have shown that bFGF is associated with osteogenic properties especially when used in combination with bone forming proteins such as BMPs [46,47]. Our present studies, however, are the first to show suppression of elastin calcification by bFGF at 28 days in subdermal implantation model; however, whether this holds true for long-term studies and in the circulatory environment is unknown and needs further study in the future.…”

Section: Discussionmentioning

confidence: 99%

In vivo cellular repopulation of tubular elastin scaffolds mediated by basic fibroblast growth factor

2007

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In vivo tissue engineering has been explored as a method to repopulate scaffolds with autologous cells to create a functional, living, and non-immunogenic tissue substitute. In this study, we describe an approach to in vivo cellular repopulation of a tissue-derived tubular elastin scaffold. Pure elastin scaffolds were prepared from porcine carotid arteries (elastin tubes). Elastin tubes were filled with agarose gel containing basic fibroblast growth factor (bFGF) to allow sustained release of growth factor. These tubes were implanted in subdermal pouches in adult rats. The elastin tubes with growth factor had significantly more cell infiltration at 28 days than those without growth factor. Immunohistochemical staining indicated that most of these cells were fibroblasts, of which a few were activated fibroblasts (myofibroblasts). Microvasculature was also observed within the scaffolds. Macrophage infiltration was seen at 7 days, which diminished by 28 days of implantation. None of the elastin tubes with bFGF calcified. These results demonstrated that the sustained release of bFGF brings about repopulation of elastin scaffolds in vivo while inhibiting calcification. Results showing myofibroblast infiltration and vascularization are encouraging since such an in vivo implantation technique could be used for autologous cell repopulation of elastin scaffolds for vascular graft applications.

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Section: Discussionmentioning

confidence: 99%

In vivo cellular repopulation of tubular elastin scaffolds mediated by basic fibroblast growth factor

2007

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“…Since recombinant human BMP-2 (rhBMP-2) became available, many animal studies have been performed examining the induction of bone formation following implantation of rhBMP-2 using various carriers. 34,36,38,46,48 Fibroblast growth factor (FGF) was originally identified from extracts of the pituitary gland and brain, and has been demonstrated to stimulate the proliferation of fibroblasts. 22 The activity was mainly attributed to two similar proteins, acidic and basic fibroblast growth factor (bFGF, also known as bFGF-2).…”

Section: Introductionmentioning

confidence: 99%

Osteogenic Responses to Different Concentrations/Ratios of BMP-2 and bFGF in Bone Formation

et al. 2009

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Recombinant human bone morphogenetic protein-2 (rhBMP-2) and basic fibroblast growth factor (bFGF) are the focus of research pertaining to the stimulation of bone formation. We ascertained the effects of different concentrations rhBMP-2 on proliferation and differentiation of bone marrow stromal cells (BMSCs) in vitro and on ectopic bone formation in rats. BMSCs were obtained from beagle dogs and cultured in medium containing different concentrations rhBMP-2 and bFGF (0, 25, 50, 100, or 200 ng/mL). In a separate experiment, BMSCs were treated with different ratios (1:1, 2:1, 4:1, or 8:1) of rhBMP to bFGF (in each case the concentration of rhBMP was 100 ng/mL and the bFGF concentrations 100, 50, 25, or 12.5 ng/mL). Proliferation and differentiation of BMSCs were quantified by assessing methyl thiazole tetrazolium (MTT) and alkaline phosphatase (ALP) over 6 consecutive days. Von Kossa staining was performed on day 6. For the in vivo tests, porous calcium phosphate cement (CPC) was seeded with BMSCs (5 x 10(4)) in medium containing 100 ng/mL rhBMP-2, 50 ng/mL bFGF or combined 100 ng/mL rhBMP-2 and 50 ng/mL bFGF. These cells were then subcutaneously implanted in four sites in nude rats. Bone formation was detected by histology at weeks 4 and 12 and quantified using a KS400 computer based image analysis system. It was determined that combined rhBMP-2 and bFGF at a ratio of 2:1 (100:50 ng/mL) promoted significantly increased BMSC proliferation and differentiation of BMSCs compared to rhBMP-2 or bFGF alone (p < 0.05). CPC with combined 100 ng/mL rhBMP-2 and 50 ng/mL bFGF stimulated more bone formation than either 100 ng/mL rhBMP-2 or 100 ng/mL bFGF (p < 0.05). These results show that a combination of rhBMP-2 and bFGF effectively induces early BMSC proliferation and differentiation in vitro. When combined, rhBMP-2 and bFGF synergistically promote new bone formation.

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“…[71][72][73] An inhibitory effect on the production of differentiation markers like alkaline phosphatase activity and induction of mineralization were also seen in cultures containing FGF-2/-9 in combination with BMP-2 in a 1:5 ratio or with osteogenic medium. 71,73,74 However, in cultures containing FGF-2 and BMP-2 at a ratio of 1:10 or higher, the combination had a stimulatory effect on the bone differentiation markers compared to BMP alone. 70 These studies suggest a ratio-dependent FGF/BMP effect in which the mitogenic FGF stimulus overrules the BMP-induced osteogenic differentiation at high FGF concentrations.…”

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confidence: 99%

Growth Factor Interactions in Bone Regeneration

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Creemers

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et al. 2010

Tissue Engineering Part B: Reviews

100

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Bone regeneration is a complex process regulated by a large number of bioactive molecules. Many growth factors and cytokines involved in the natural process of bone healing have been identified and tested as potential therapeutic candidates to enhance the regeneration process. Although many of these studies show an enhancement of the bone regeneration process by a single drug therapy, in vivo bone regeneration is the result of a complex interplay between the applied growth factor and various endogenous produced growth factors. To investigate these growth factor interactions, various studies have investigated the effect of growth factor combinations on bone regeneration. This review provides an overview of the growth factor and cytokine combinations tested in translational bone regeneration studies and shows that their interaction may result in an enhancement or inhibition of bone formation.

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In Vitro Osteogenic Response of Rat Bone Marrow Cells to bFGF and BMP-2 Treatments

Cited by 58 publications

References 35 publications

In vivo cellular repopulation of tubular elastin scaffolds mediated by basic fibroblast growth factor

In vivo cellular repopulation of tubular elastin scaffolds mediated by basic fibroblast growth factor

Osteogenic Responses to Different Concentrations/Ratios of BMP-2 and bFGF in Bone Formation

Growth Factor Interactions in Bone Regeneration

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