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

BackgroundLarge 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.ResultsCritical-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 (107, 105, 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 107 and 105 cells groups compared with the 0 cells groups. By quantitative CT, the bone mineral density was higher in the 560 μg with 107 and 105 cells groups, while non-uniformity of the bone mineral density was improved in the 560 μg with 107 and 105 cells groups and 140 μg/107 cells group. Mechanically, the maximum loads at failure were significantly higher in the 560 μg with 107 and 105 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 107 and 105 cells and 140 μg with 107 and 105 cells groups.ConclusionsImplantation 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 BackgroundLarge 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.ResultsCritical-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 (107, 105, 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 107 and 105 cells groups compared with the 0 cells groups. By quantitative CT, the bone mineral density was higher in the 560 μg with 107 and 105 cells groups, while non-uniformity of the bone mineral density was improved in the 560 μg with 107 and 105 cells groups and 140 μg/107 cells group. Mechanically, the maximum loads at failure were significantly higher in the 560 μg with 107 and 105 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 107 and 105 cells and 140 μg with 107 and 105 cells groups.ConclusionsImplantation 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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37 schema:keywords CT
38 ConclusionsImplantation
39 Escherichia coli-derived recombinant human bone morphogenetic protein-2
40 Escherichia coli-derived rhBMP-2
41 Mechanically
42 animals
43 assistance
44 autologous bone marrow-derived mesenchymal stromal cells
45 beagle dogs
46 beagles
47 bone
48 bone formation
49 bone healing
50 bone marrow-derived mesenchymal stromal cells
51 bone mineral density
52 bone morphogenetic protein-2
53 bone regeneration
54 bone width
55 canine
56 cavity
57 cell groups
58 cell number
59 cells
60 combination
61 combined implantation
62 control group
63 critical-sized defects
64 defects
65 density
66 dogs
67 effect
68 experimental animals
69 factors
70 failure
71 female beagle dogs
72 female beagles
73 forelimb
74 formation
75 group
76 healing
77 healthy female beagle dogs
78 human bone morphogenetic protein-2
79 implantation
80 improved bone mineral density
81 load
82 marrow cavity
83 marrow-derived mesenchymal stromal cells
84 maximum load
85 mesenchymal stromal cells
86 mineral density
87 morphogenetic protein-2
88 number
89 osteoblasts
90 osteoclasts
91 osteoinductive factors
92 osteoprogenitor cells
93 present
94 previous studies
95 promotion
96 protein 2
97 quantitative CT
98 recombinant human bone morphogenetic protein-2
99 regenerated bone
100 regeneration
101 segmental defects
102 stromal cells
103 study
104 transplantation
105 treatment groups
106 ulna
107 ulnar
108 ulnar defects
109 vessels
110 weeks
111 width
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