Synergistic enhancement of bone formation and healing by stem cell–expressed VEGF and bone morphogenetic protein-4

Peng, Hairong; Wright, Vonda J.; Ūsas, Arvydas; Gearhart, Brian; Shen, Horng-Der; Cummins, James; Huard, Johnny

doi:10.1172/jci15153

Cited by 645 publications

(535 citation statements)

References 30 publications

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“…Combined use of VEGF and BMP-2 [19,24,34,35,37,40] and BMP-4 [20,25,36] showed synergistic effects in osteogenesis. It has been shown that combined use of VEGF with one of the most potent BMPs, BMP-6 [23,26], enhances osteogenesis and angiogenesis of mouse bone marrow stem cells in vitro and in vivo [8], however, the effectiveness of this therapy for ON has not been determined.…”

Section: Questions/hypothesesmentioning

confidence: 95%

“…Direct VEGF administration can improve blood flow and neovascularization in necrotic bone [38]. In addition to its effects on angiogenesis, VEGF plays an important role in bone growth and repair by interacting with other growth factors [35,36]. However, overexpression of VEGF actually can adversely affect osteogenesis and decrease bone formation [25,[34][35][36][37].…”

Section: Limitationsmentioning

confidence: 99%

“…In addition to its effects on angiogenesis, VEGF plays an important role in bone growth and repair by interacting with other growth factors [35,36]. However, overexpression of VEGF actually can adversely affect osteogenesis and decrease bone formation [25,[34][35][36][37]. In our in vitro study, the optimal ratio of VEGF and BMP-6 will be determined so that the undesired effects of VEGF can be avoided in the in vivo study.…”

Section: Limitationsmentioning

confidence: 99%

“…Stem cell-mediated bone regeneration augmented with combined use of VEGF and BMPs has been reported but only for BMP-2 [19,24,34,35,37,40] and BMP-4 [20,25,36]. It has been shown that VEGF enhances BMP-6-induced osteogenesis of mouse stem cells in vitro and in vivo, however, the effectiveness of this therapy for ON has not been determined [8].…”

Section: Next Stepsmentioning

confidence: 99%

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Emerging Ideas: Treatment of Precollapse Osteonecrosis Using Stem Cells and Growth Factors

Cui

Botchwey

2011

Clinical Orthopaedics &Amp; Related Research

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Section: Questions/hypothesesmentioning

confidence: 95%

Section: Limitationsmentioning

confidence: 99%

Section: Limitationsmentioning

confidence: 99%

Section: Next Stepsmentioning

confidence: 99%

See 2 more Smart Citations

Emerging Ideas: Treatment of Precollapse Osteonecrosis Using Stem Cells and Growth Factors

Cui

Botchwey

2011

Clinical Orthopaedics &Amp; Related Research

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“…The vascular endothelial growth factor (VEGF) has an essential role in angiogenesis and bone regeneration (Carano and Filvaroff, 2003). Muscle-derived stem cells modified with VEGF show no effect, whereas with both rhBMP-4 and VEGF, the stem cells augment cartilage formation in the early stages of endochondral bone formation (Peng et al, 2002), indicating the necessary coexistence of bone-specific growth factor in VEGF gene therapy. Osteoactivin gene is an osteoblast-specific gene in bone, positively regulating osteoblast differentiation Selim et al, 2003;Abdelmagid et al, 2007Abdelmagid et al, , 2008.…”

Section: Potential Candidate Genesmentioning

confidence: 99%

Genetically Engineered Mesenchymal Stem Cells: The Ongoing Research for Bone Tissue Engineering

Hong

Chen²,

et al. 2010

The Anatomical Record

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Bone grafting is crucial in the surgical treatment of bone defects and nonunion fractures. Autogenous bone, allogenous bone, and biomaterial scaffold are three main sources of bone grafts. The biomaterial scaffold, both natural and synthetic, is widely accessible but weak in osteogenic potential. One approach to solve this problem is cell-based bone tissue engineering (BTE), established by growing living osteogenic cells on scaffold in vitro to build up its osteoinducitive capability. Mesenchymal stem cell (MSC) is suitable for use in cell-based BTE, but it remains a considerable challenge to induce MSCs to form solely bone and while preventing MSCs from differentiating into fats, muscles, and possibly neural elements in vivo. Recently, there is a drastic rise in use of genetically engineered MSCs, which can secrete growth factors or alter the transcription level, leading to osteoblast lineage commitment, bone formation, fracture repair, and spinal fusion. In this article, we reviewed the literatures regarding applications of genetically engineered MSCs in BTE. We addressed the currently applicable genes and candidate genes for MSCs modification, transduction efficiency and safety issues of the transfect vectors, and administration routes, and we briefly described in vivo tracking and potential clinical application of the genetically modified MSCs in BTE. Anat Rec, 293:531-537, 2010. V V C 2009 Wiley-Liss, Inc.

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In Vitro Effects of Combined and Sequential Bone Morphogenetic Protein Administration

Arosarena

Puleo

2007

Archives of Facial Plastic Surgery

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Objective: To assess the effects of combined and sequential administration of bone morphogenetic protein 2 (BMP-2) and BMP-7 on osteoblastic differentiation compared with administration of single growth factors.Design: In vitro study of osseous differentiation in murine pluripotent cells using assays of extracellular matrix calcification, alkaline phosphatase activity, and expression of osseous markers. Mesenchymal cells were cultured with BMP-2, BMP-7, or a combination of these growth factors or were sequentially exposed to the growth factors.Results: Sequential administration of BMP-2 and BMP-7 resulted in increased extracellular matrix calcification and expression of osteocalcin, whereas all groups treated with BMP up-regulated expression of the osteoblastic transcription factor Runx2/cbfa1, type I collagen, and the inhibitory BMP second messenger Smad6. None of the experimental groups demonstrated increased expression of osteopontin or Smad1, and only cells treated with concurrent administration of BMP-2 and BMP-7 increased Smad5 expression. Alkaline phosphatase activity was increased from baseline only in cells treated with BMP-2 alone.Conclusions: Culture with BMP-2 and BMP-7, their sequential administration, and their coadministration had variable effects on osseous differentiation in mesenchymal cells. These results demonstrate the need for increased understanding of the role of growth factors and their combinations in bone development and have important implications for the ongoing development of osteoinductive therapies.Arch Facial Plast Surg. 2007;9(4):242-247

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Synergistic enhancement of bone formation and healing by stem cell–expressed VEGF and bone morphogenetic protein-4

Cited by 645 publications

References 30 publications

Emerging Ideas: Treatment of Precollapse Osteonecrosis Using Stem Cells and Growth Factors

Emerging Ideas: Treatment of Precollapse Osteonecrosis Using Stem Cells and Growth Factors

Genetically Engineered Mesenchymal Stem Cells: The Ongoing Research for Bone Tissue Engineering

In Vitro Effects of Combined and Sequential Bone Morphogenetic Protein Administration

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