Escherichia coli-derived recombinant human bone morphogenetic protein-2 combined with bone marrow-derived mesenchymal stromal cells improves bone regeneration in canine segmental ... View Full Text


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Article Info

DATE

2016-09-13

AUTHORS

Takamasa Itoi, Yasuji Harada, Hiroyuki Irie, Michiko Sakamoto, Katsutoshi Tamura, Takuya Yogo, Satoshi Soeta, Hajime Amasaki, Yasushi Hara, Masahiro Tagawa

ABSTRACT

BACKGROUND: Large bone defects in canines usually require assistance to achieve healing. Implantation of osteoinductive factors can promote bone healing, while transplantation of osteoprogenitor cells can enhance bone regeneration. We hypothesized that implantation of an osteoinductive factor, recombinant human bone morphogenetic protein-2 (rhBMP-2), combined with osteoprogenitor cells, bone marrow-derived mesenchymal stromal cells (BMSCs), would synergistically promote bone healing. In this study, we examined the combined effects of Escherichia coli-derived rhBMP-2 and BMSCs on bone healing after implantation into canine ulnar defects. RESULTS: Critical-sized osteoperiosteal segmental defects (2.5 cm) were created in the ulnae of healthy female beagle dogs, and implanted with combinations of E. coli-derived rhBMP-2 (560 or 140 μg) and autologous BMSCs (10(7), 10(5), or 0 cells). In the present study,18 forelimbs of nine healthy purpose-bred female beagles were used. All six treatment groups contained three forelimbs, and the animals were euthanized after 12 weeks. The control groups (560 and 140 μg/0 cells) were cited from our previous study to reduce the number of experimental animals. Radiographically, the regenerated bone width was significantly increased in the 560 or 140 μg with 10(7) and 10(5) cells groups compared with the 0 cells groups. By quantitative CT, the bone mineral density was higher in the 560 μg with 10(7) and 10(5) cells groups, while non-uniformity of the bone mineral density was improved in the 560 μg with 10(7) and 10(5) cells groups and 140 μg/10(7) cells group. Mechanically, the maximum loads at failure were significantly higher in the 560 μg with 10(7) and 10(5) cells groups. Histologically, the regenerated bone was well-developed and contained osteocyte-like cells marrow cavities, and vessels. However, the osteoclasts and osteoblasts were hardly observed. The osteocyte-like cell numbers were significantly higher in the 560 μg with 10(7) and 10(5) cells and 140 μg with 10(7) and 10(5) cells groups. CONCLUSIONS: Implantation of E. coli-derived rhBMP-2 and BMSCs led to significantly enhanced bone formation, with improved bone mineral density and reduced non-uniformity of the regenerated bone. Combined implantation of rhBMP-2 and BMSCs may be useful for promotion of bone healing in critical-sized defects in canines. More... »

PAGES

201

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/s12917-016-0829-y

DOI

http://dx.doi.org/10.1186/s12917-016-0829-y

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1027636759

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/27619812


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31 schema:description BACKGROUND: Large bone defects in canines usually require assistance to achieve healing. Implantation of osteoinductive factors can promote bone healing, while transplantation of osteoprogenitor cells can enhance bone regeneration. We hypothesized that implantation of an osteoinductive factor, recombinant human bone morphogenetic protein-2 (rhBMP-2), combined with osteoprogenitor cells, bone marrow-derived mesenchymal stromal cells (BMSCs), would synergistically promote bone healing. In this study, we examined the combined effects of Escherichia coli-derived rhBMP-2 and BMSCs on bone healing after implantation into canine ulnar defects. RESULTS: Critical-sized osteoperiosteal segmental defects (2.5 cm) were created in the ulnae of healthy female beagle dogs, and implanted with combinations of E. coli-derived rhBMP-2 (560 or 140 μg) and autologous BMSCs (10(7), 10(5), or 0 cells). In the present study,18 forelimbs of nine healthy purpose-bred female beagles were used. All six treatment groups contained three forelimbs, and the animals were euthanized after 12 weeks. The control groups (560 and 140 μg/0 cells) were cited from our previous study to reduce the number of experimental animals. Radiographically, the regenerated bone width was significantly increased in the 560 or 140 μg with 10(7) and 10(5) cells groups compared with the 0 cells groups. By quantitative CT, the bone mineral density was higher in the 560 μg with 10(7) and 10(5) cells groups, while non-uniformity of the bone mineral density was improved in the 560 μg with 10(7) and 10(5) cells groups and 140 μg/10(7) cells group. Mechanically, the maximum loads at failure were significantly higher in the 560 μg with 10(7) and 10(5) cells groups. Histologically, the regenerated bone was well-developed and contained osteocyte-like cells marrow cavities, and vessels. However, the osteoclasts and osteoblasts were hardly observed. The osteocyte-like cell numbers were significantly higher in the 560 μg with 10(7) and 10(5) cells and 140 μg with 10(7) and 10(5) cells groups. CONCLUSIONS: Implantation of E. coli-derived rhBMP-2 and BMSCs led to significantly enhanced bone formation, with improved bone mineral density and reduced non-uniformity of the regenerated bone. Combined implantation of rhBMP-2 and BMSCs may be useful for promotion of bone healing in critical-sized defects in canines.
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39 Critical-sized osteoperiosteal segmental defects
40 Escherichia coli-derived recombinant human bone morphogenetic protein-2
41 Escherichia coli-derived rhBMP-2
42 Mechanically
43 animals
44 assistance
45 autologous bone marrow-derived mesenchymal stromal cells
46 beagle dogs
47 beagles
48 bone
49 bone defects
50 bone formation
51 bone healing
52 bone marrow-derived mesenchymal stromal cells
53 bone mineral density
54 bone morphogenetic protein-2
55 bone regeneration
56 bone width
57 canine
58 canine segmental ulnar
59 canine ulnar defects
60 cavity
61 cell groups
62 cell number
63 cells
64 cells marrow cavities
65 coli-derived recombinant human bone morphogenetic protein-2
66 coli-derived rhBMP-2
67 combination
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69 control group
70 critical-sized defects
71 defects
72 density
73 dogs
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76 factors
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78 female beagle dogs
79 female beagles
80 forelimb
81 formation
82 group
83 healing
84 healthy female beagle dogs
85 healthy purpose-bred female beagles
86 human bone morphogenetic protein-2
87 implantation
88 improved bone mineral density
89 large bone defects
90 load
91 marrow cavity
92 marrow-derived mesenchymal stromal cells
93 maximum load
94 mesenchymal stromal cells
95 mineral density
96 morphogenetic protein-2
97 number
98 osteoblasts
99 osteoclasts
100 osteocyte-like cell numbers
101 osteocyte-like cells marrow cavities
102 osteoinductive factors
103 osteoperiosteal segmental defects
104 osteoprogenitor cells
105 present
106 previous studies
107 promotion
108 protein 2
109 purpose-bred female beagles
110 quantitative CT
111 recombinant human bone morphogenetic protein-2
112 regenerated bone
113 regenerated bone width
114 regeneration
115 segmental defects
116 segmental ulnar
117 stromal cells
118 study
119 transplantation
120 treatment groups
121 ulna
122 ulnar
123 ulnar defects
124 vessels
125 weeks
126 width
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