Osteogenic graft vascularization and bone resorption by VEGF-expressing human mesenchymal progenitors

Helmrich, Uta; Maggio, Nunzia Di; Güven, Sinan; Groppa, Elena; Melly, Ludovic; Largo, René D.; Heberer, Michael; Martin, Ivan; Scherberich, Arnaud; Banfi, Andrea

doi:10.1016/j.biomaterials.2013.03.040

Cited by 80 publications

(64 citation statements)

References 47 publications

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“…101 Another genetic modification strategy involved modifying MSCs to express VEGF. 102 The increased expression of VEGF led to a threefold increase of vascular density compared with control MSC-seeded grafts. However, the increased VEGF levels resulted in decreased quantities of bone formation and increased osteoclast populations.…”

Section: Genetic Modification Of Mscsmentioning

confidence: 96%

Mesenchymal Stem Cells: Roles and Relationships in Vascularization

Melchiorri

Nguyen

Fisher

2014

Tissue Engineering Part B: Reviews

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Section: Genetic Modification Of Mscsmentioning

confidence: 96%

Mesenchymal Stem Cells: Roles and Relationships in Vascularization

Melchiorri

Nguyen

Fisher

2014

Tissue Engineering Part B: Reviews

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“…Therefore, the equilibrium between VEGF triggered angiogenesis, osteogenesis and bone resorption needs to be carefully investigated in controlled models to devise rational strategies that exploit the pro-angiogenic potency of VEGF expression for a clinical application. Helmrich et al 54) stressed in his work that in minimizing cell expansion, the osteogenic differentiation potential of bone marrow-MSCs was maintained, but a strong reduction in bone formation was observed when the VEGF gene over-expressed. VEGF has been reported to participate in several stages of bone repair and regeneration; however, most studies have primarily examined the consequences for bone repair when VEGF levels were manipulated at local injury sites or systemically 55) .…”

Section: Discussionmentioning

confidence: 99%

Osteoinductive Activity of Bone Scaffold Bioceramic Companied with Control Release of VEGF Protein Treated Dental stem cells as A New Concept for Bone Regeneration: Part II

Enezei

Afsari

Takeuchi

et al. 2018

J. Hard Tissue Biology.

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In bone tissue engineering, angiogenesis is closely associated with osteogenesis where reciprocal interactions between endothelial and osteoblast cells play an important role in bone regeneration. Over-expression of the angiogenesisrelated gene due to a higher dose of vascular endothelial growth factor (VEGF) protein can inhibit osteogenesis process at mRNA level. To study the eff ect of controlled released of the VEGF protein incorporating fi brin glue (FG) treated with fabricated porous biphasic calcium phosphate (BCP) on osteogenesis gene (BMP-2) and angiogenesis gene (VEGF) on dental stem cells (DSCs) at mRNA level. DSCs were treated with two diff erent modalities; VEGF protein incorporated FG, and VEGF protein incorporated FG added-BCP treated media. The cells were harvested at four diff erent time intervals (day 3, day 7, day 10 and day 14) and were subjected to RNA isolation using the RNA extraction kit. This was followed by performing one step-reverse transcriptase-PCR (RT-PCR) to amplify the osteogenesis BMP-2 gene, angiogenesis VEGF gene and the osteoblast-specifi c transcription factor expression Osterix (Osx) with and without the controlled release of VEGF protein. The RT-PCR products were then electrophoresed. The gel image was captured using Image Analyser. Controlled release of VEGF protein using FG as a natural delivery system, using a single growth factor, show a signifi cantly enhanced osteogenesis BMP-2 gene and angiogenesis VEGF gene with a high expression of Osx compare with non-delivered free VEGF protein treated groups. FG is a biocompatible material that could be employed as a delivery vehicle for controlled release of VEGF protein single or dual release in bone tissue engineering strategy and design of the study. Application of this method for using FG is mixing with a porous ceramic scaff old loading with the growth factors is a convenient and promising strategy for improving osteogenesis and angiogenesis processes of reconstruction critical-sized bone defects and might change the scope of modern surgery.

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“…Threshold dose of VEGF level for normal angiogenesis can be induced over a wide range because control expression at moderate levels might induce eff ective vascularization while limiting osteogenesis achieved 33) .…”

Section: Discussionmentioning

confidence: 99%

Enhanced Osteogenic and Angiogenic-Related Gene Expression of Human Dental Stem Cells on Biphasic Calcium Phosphate Scaffold Treated with Vascular Endothelial Growth Factor: Part I

Enezei

Ahmad

Khamis

et al. 2017

J. Hard Tissue Biology.

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To study the eff ectiveness of vascular endothelial growth factor (VEGF) added with biphasic calcium phosphate (BCP) on the expression of osteogenesis and angiogenesis-related gene in dental stem cells (DSCs). The cells were treated with three diff erent modalities; BCP group, VEGF group, and VEGF-added-BCP. The optimal BCP and VEGF concentrations were determined. The cells were harvested at four diff erent time intervals (day 3, day 7, day 10 and day 14) and were subjected to RNA isolation. Osteogenesis and angiogenesis-regulated genes was amplifi ed using reverse transcriptase-PCR (RT-PCR). The RT-PCR products were then electrophoresed. The gel images were captured using Image Analyser AlphaEaseFC™. Angiogenesis and osteogenesis genes were clearly expressed in DSCs in response to treatments with 75mg/ml BCP and 5ng/ml VEGF. Angiogenesis gene VEGF was highly expressed by VEGF treatment group but showed some changes when added with BCP. Osteogenesis genes (BMP-2 and OPN) were positively aff ected by both BCP and VEGF. Some genes were expressed at an earlier time interval compared to the other genes depending on the type of treatments. BCP treatment induced high expression of initial-regulated osteogenesis genes (BMP-2 and OPN). Combination of BCP and VEGF modality on DSCs was suggested to initiate osteogenesis and angiogenesis-related gene expressions earlier than the other modalities. In our design, uncontrolled release of VEGF protein showed inhibition of BMP-2 at mRNA level in VEGF-BCP combined group.

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Osteogenic graft vascularization and bone resorption by VEGF-expressing human mesenchymal progenitors

Cited by 80 publications

References 47 publications

Mesenchymal Stem Cells: Roles and Relationships in Vascularization

Mesenchymal Stem Cells: Roles and Relationships in Vascularization

Osteoinductive Activity of Bone Scaffold Bioceramic Companied with Control Release of VEGF Protein Treated Dental stem cells as A New Concept for Bone Regeneration: Part II

Enhanced Osteogenic and Angiogenic-Related Gene Expression of Human Dental Stem Cells on Biphasic Calcium Phosphate Scaffold Treated with Vascular Endothelial Growth Factor: Part I

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