Autologous bone grafts with MSCs or FGF-2 accelerate bone union in large bone defects.

Nobuo Adachi,Tomoyuki Nakasa,Mitsuo Ochi,Masakazu Ishikawa,Hiroaki Murakami

doi:10.1186/s13018-016-0442-6

Nobuo Adachi, Tomoyuki Nakasa + Show 3 more

Open Access

https://doi.org/10.1186/s13018-016-0442-6

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Abstract

BacgroundAlthough the contribution of fibroblast growth factor (FGF)-2 and mesenchymal stromal cells (MSCs) to bone formation is well known, few studies have investigated the combination of an autologous bone graft with FGF-2 or MSCs for large bone defects.MethodsWe studied an atrophic non-union model with a large bone defect, created by resecting a 10-mm section from the center of each femoral shaft of 12-week-old Sprague-Dawley rats. The periosteum of the proximal and distal ends of the femur was cauterized circumferentially, and excised portions were used in the contralateral femur as autologous bone grafts. The rats were randomized to three groups and given no further treatment (group A), administered FGF-2 at 20 μg/20 μL (group B), or 1.0 × 106 MSCs (group C). Radiographs were taken every 2 weeks up to 12 weeks, with CT performed at 12 weeks. Harvested femurs were stained with toluidine blue and evaluated using radiographic and histology scores.ResultsRadiographic and histological evaluation showed that bone union had been achieved at 12 weeks in group C, while group B showed callus formation and bridging callus but non-union, and in group A, callus formation alone was evident. Both radiographic and histological scores were significantly higher at 2, 4, 6, 8, 10, and 12 weeks in groups B and C than group A and also significantly higher in group C than group B at 12 weeks.ConclusionsThese data suggest that autologous bone grafts in combination with MSCs benefit difficult cases which cannot be treated with autologous bone grafts alone.

Highlights

For bone defects or non-union, autologous bone grafts are used daily in clinical practice
The bone marrow was flushed out of the femoral and tibial marrow cavities of rats with a 21-gauge needle connected to a 10-mL syringe containing 10 mL of culture medium composed of high-glucose Dulbecco’s modified Eagle’s medium (DMEM; Life Technologies, Grand Island, NY, USA), 10 % heat-inactivated fetal bovine serum
For the treatment of a bone defect or non-union, autologous bone grafting is recognized as the gold standard method, and good results have been obtained in the clinical setting

Summary

Introduction

For bone defects or non-union, autologous bone grafts are used daily in clinical practice. Autologous bone grafting is the gold standard, its ability to achieve bone union under relatively poor conditions in the recipient site such as large bone defects or atrophic non-union is not promising. An autologous bone graft contains cells including bone marrow mesenchymal stem cells (MSCs) and several growth factors which induce bone formation in a native bone structure. This raises the possibility that augmentation of these factors could enhance the ability of a graft to achieve bone union even under poor conditions. Members of the fibroblast growth factor (FGF) family, which comprises 23 subtypes, are present in most tissues throughout the body and exert a variety of physiological effects, while their abnormal expression causes human genetic diseases such as achondroplasia or thanatophoric dysplasia [1].

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