Department of Orthopedic Surgery, University Hospital Grosshadern, Munich, Germany.
Tissue Eng Part A. 2010 Mar;16(3):1093-101. doi: 10.1089/ten.TEA.2009.0656.
The repair of bone defects can be induced experimentally with bone morphogenetic protein-2 (BMP-2) producing fat-derived stem cells, but this ex vivo tissue engineering method requires the isolation and long-term culture of autologous cells. To develop an expedited bone repair strategy, we transferred BMP-2 cDNA directly to autologous fat tissue fragments that were held in culture for only 24 h before implantation. We evaluated the ability of such gene-activated fat grafts to regenerate large segmental bone defects in rats. Fat tissue was harvested from 2 of 35 male Fischer 344 rats used for this study. The fat tissue fragments were incubated with an adenoviral vector carrying the cDNA encoding either BMP-2 or green florescent protein (GFP), or they remained unmodified. According to their group, the segmental femoral bone defects of 33 rats were filled press fit with either BMP-2-activated fat tissue, GFP-transduced fat tissue, or unmodified fat tissue. Another control group remained untreated. Femora were evaluated by radiographs, microcomputed tomography, biomechanical torsional testing, and histology. Radiographically and histologically, 100% of the femora treated with BMP-2-activated fat grafts were bridged at 6 weeks after surgery. The femora of this group exceeded the bone volume and the biomechanical stability of intact, contralateral femora. Control defects receiving no treatment, unmodified fat tissue, or GFP-transduced fat were filled with fibrous or adipose tissue, as evaluated by histology. The use of BMP-2 gene-activated fat tissue grafts represents an expedited and effective bone repair strategy that does not require the extraction and expansion of stem cells.
骨形态发生蛋白-2（BMP-2）产生的脂肪源性干细胞可诱导实验性骨缺损修复，但这种体外组织工程方法需要分离和长期培养自体细胞。为了开发一种快速的骨修复策略，我们将 BMP-2 cDNA 直接转染到自体脂肪组织碎片中，这些组织碎片在植入前仅在培养中培养 24 小时。我们评估了这种基因激活脂肪移植物再生大鼠大节段骨缺损的能力。这项研究使用了 35 只雄性 Fischer 344 大鼠中的 2 只来获取脂肪组织。将脂肪组织碎片与携带编码 BMP-2 或绿色荧光蛋白（GFP）的 cDNA 的腺病毒载体孵育，或者保持未修饰。根据分组，33 只大鼠的节段股骨骨缺损被紧密贴合地填充了 BMP-2 激活的脂肪组织、GFP 转导的脂肪组织或未修饰的脂肪组织。另一个对照组未接受治疗。通过 X 线照片、微计算机断层扫描、生物力学扭转试验和组织学评估股骨。X 线照片和组织学显示，手术后 6 周，用 BMP-2 激活的脂肪移植物治疗的股骨 100%桥接。该组的股骨超过了完整对侧股骨的骨体积和生物力学稳定性。未接受治疗、未修饰的脂肪组织或 GFP 转导的脂肪组织的对照缺损用纤维组织或脂肪组织填充，通过组织学评估。使用 BMP-2 基因激活的脂肪组织移植物代表了一种快速有效的骨修复策略，不需要提取和扩增干细胞。
