The effect of recombinant human bone morphogenetic protein-2 on the osteogenic potential of rat mesenchymal stem cells after several passages

Ishikawa, H.; Kitoh, Hiroshi; Sugiura, Fumiaki; Ishiguro, Naoki

doi:10.1080/17453670710013816

Cited by 42 publications

(30 citation statements)

References 28 publications

(26 reference statements)

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“…However, the proportions of newly formed bone, soft tissue, and grafted area between the two studies were similar in the DDM group. Dentin and bone have similar compositions, consisting of 18% collagen, 70% hydroxyapatite, and 2% noncollagenous protein [24]. Besides the type I collagens in dentin, microporous dentinal tubules can seize BMP solution and widen the contact area with proteins which can facilitate the continuous binding and release of BMPs [19,44].…”

Section: Discussionmentioning

confidence: 99%

“…Thus, mesenchymal stem cells are essential for the bone healing process, and mesenchymal stem cell markers such as CXCR4, CD106, CD146, OCT-4, NANOG, CD34, CD146 and CD105 are upregulated at bone healing sites [43]. rhBMP-2 has been utilized to stimulate osteoblastic proliferation from mesenchymal stem cells and accelerates bone regeneration [24]. Although numerous bone morphogenetic protein (BMP) carriers have been tested, such as collagen, demineralized bovine bone, and hydroxyapatite, these carriers have several shortcomings, such as rapid resorption, lack of long-term maintenance of volume, and incompetent release of BMP.…”

Section: Discussionmentioning

confidence: 99%

“…A rhBMP-2 is a potent osteoinductive protein which promotes the differentiation of osteoblasts from mesenchymal stem cells and accelerates bone regeneration [24]. The osteoconduction of rhBMP-2 has been widely studied in various bone healing environments, and rhBMP-2 has been shown to heal critical-sized bone defects in animal models and clinical trials [25,26].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Volumetric, Radiographic, and Histologic Analyses of Demineralized Dentin Matrix Combined with Recombinant Human Bone Morphogenetic Protein-2 for Ridge Preservation: A Prospective Randomized Controlled Trial in Comparison with Xenograft

et al. 2018

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Featured Application: Novel technology of bone regeneration.Abstract: The aim of this study was to evaluate the clinical, volumetric, radiographic, and histologic aspects of autogenous demineralized dentin matrix (DDM) combined with recombinant human bone morphogenetic protein-2 (rhBMP-2) used for ridge preservation, compared to those of deproteinized bovine bone with collagen (DBBC). Following atraumatic extraction, the socket was filled with DBBC, DDM, or rhBMP-2/DDM. Scanned images of dental casts and cone beam computed tomographs (CBCT) were superimposed for the calculation of soft and hard tissue volume alteration. Preoperative and postoperative measurements of the height and width of the alveolar ridge were compared using CBCT images. After 4 months, bone specimens were harvested for histomorphometric assessment. Loss of hard and soft tissue volume occurred at 4 months after extraction and ridge preservation in all groups. No volumetric differences were detected among the three groups before and 4 months after ridge preservation. The reduction in the horizontal width at 5 mm was higher in the DBBC compared to the DDM. Histologically, approximately 40% newly formed bone was founded in rhBMP-2/DDM group. The autogenous dentin matrix used to fill the socket was as beneficial for ridge preservation as conventional xenografts. The combination of rhBMP-2 with dentin matrix also demonstrated appreciable volumetric stability and higher new bone formation compared to DDM alone and DBBC.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Volumetric, Radiographic, and Histologic Analyses of Demineralized Dentin Matrix Combined with Recombinant Human Bone Morphogenetic Protein-2 for Ridge Preservation: A Prospective Randomized Controlled Trial in Comparison with Xenograft

et al. 2018

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“…These results suggest that the pCEP4-BMP2/7-PTD plasmid was inserted into the stable cell line (Fig. 2A) Cell-based tissue-engineering tools and methods create new opportunities that might be useful in potential clinical applications [14]. For the development of bone tissue in scaffolds, progenitor cells require continuous stimulation by osteogenic growth factors.…”

Section: Resultsmentioning

confidence: 99%

Establishment of a Stable Cell Line Expressing Human BMP2/7-PTD for Efficient Osteogenic Induction

Park¹,

Kang²,

Goo³

et al. 2012

Journal of Life Science

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Heterodimeric recombinant human bone morphogenetic proteins (rhBMPs) are powerful tools for bone tissue engineering. However, BMPs have several important limitations in their application to bone regeneration. BMPs have a short half-life and must be used in high concentrations, which may be cost-inefficient. To overcome these problems, we established a stable cell line that expressed the fusion protein comprised of recombinant human BMP2/7 heterodimer protein and PTD (rhBMP2/7-PTD). This stable cell line enabled high process yields by continuously expressing rhBMP2/7-PTD products at high levels throughout cultivation. This synthesized BMP7 was fused to a BMP2 protein with four glycine residues (to allow free bond rotation of the domains) and PTD. To demonstrate that the rhBMP2/7-PTD protein that was secreted from an rhBMP2/7-PTD-expressing stable cell line exhibited biological activity consistent with its role as an osteogenic differentiation induction growth factor, we evaluated BMP-induced ALP activity. Our results suggest that this cell line may be a powerful and efficient tool for applications such as bone tissue regeneration.

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“…Mesenchymal stem cells (MSCs) have been considered an important cell line for bone tissue engineering, and are capable of undergoing differentiation into a variety of specialized mesenchymal tissues including bone, tendon, cartilage, muscle, ligament, fat, and marrow stroma (Sugiura et al, 2004;Ishikawa et al, 2007). These are prevalent in bone marrow, even in adults, and have been widely used in tissue engineering to promote bone regeneration (Tae et al, 2006;Cordonnier et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Tissue-engineered composite scaffold of poly(lactide-co-glycolide) and hydroxyapatite nanoparticles seeded with autologous mesenchymal stem cells for bone regeneration

Zhang

Wang

et al. 2017

J. Zhejiang Univ. Sci. B

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Abstract:Objective: A new therapeutic strategy using nanocomposite scaffolds of grafted hydroxyapatite (g-HA)/ poly(lactide-co-glycolide) (PLGA) carried with autologous mesenchymal stem cells (MSCs) and bone morphogenetic protein-2 (BMP-2) was assessed for the therapy of critical bone defects. At the same time, tissue response and in vivo mineralization of tissue-engineered implants were investigated. Methods: A composite scaffold of PLGA and g-HA was fabricated by the solvent casting and particulate-leaching method. The tissue-engineered implants were prepared by seeding the scaffolds with autologous bone marrow MSCs in vitro. Then, mineralization and osteogenesis were observed by intramuscular implantation, as well as the repair of the critical radius defects in rabbits. Results: After eight weeks post-surgery, scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDX) revealed that g-HA/PLGA had a better interface of tissue response and higher mineralization than PLGA. Apatite particles were formed and varied both in macropores and micropores of g-HA/PLGA. Computer radiographs and histological analysis revealed that there were more and more quickly formed new bone formations and better fusion in the bone defect areas of g-HA/PLGA at 2-8 weeks post-surgery. Typical bone synostosis between the implant and bone tissue was found in g-HA/PLGA, while only fibrous tissues formed in PLGA. Conclusions: The incorporation of g-HA mainly improved mineralization and bone formation compared with PLGA. The application of MSCs can enhance bone formation and mineralization in PLGA scaffolds compared with cell-free scaffolds. Furthermore, it can accelerate the absorption of scaffolds compared with composite scaffolds.

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The effect of recombinant human bone morphogenetic protein-2 on the osteogenic potential of rat mesenchymal stem cells after several passages

Abstract: From our results, osteogenic potential can be maintained even in BMSCs that have been passaged several times in the presence of rhBMP-2. These cells are capable of inducing and participating in bone formation and can be used for clinical applications.

Cited by 42 publications

References 28 publications

Volumetric, Radiographic, and Histologic Analyses of Demineralized Dentin Matrix Combined with Recombinant Human Bone Morphogenetic Protein-2 for Ridge Preservation: A Prospective Randomized Controlled Trial in Comparison with Xenograft

Volumetric, Radiographic, and Histologic Analyses of Demineralized Dentin Matrix Combined with Recombinant Human Bone Morphogenetic Protein-2 for Ridge Preservation: A Prospective Randomized Controlled Trial in Comparison with Xenograft

Establishment of a Stable Cell Line Expressing Human BMP2/7-PTD for Efficient Osteogenic Induction

Tissue-engineered composite scaffold of poly(lactide-co-glycolide) and hydroxyapatite nanoparticles seeded with autologous mesenchymal stem cells for bone regeneration

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