Cui Quanjun, Xiao Zengming, Li Xudong, Saleh Khaled J, Balian Gary
Department of Orthopaedic Surgery, Orthopaedic Research Laboratories, University of Virginia School of Medicine, Box 800159, Charlottesville, VA 22908, USA.
J Bone Joint Surg Am. 2006 Nov;88 Suppl 3:167-72. doi: 10.2106/JBJS.F.00891.
Treatment of osteonecrosis continues to be a challenging problem. The replacement of necrotic bone with graft materials that promote osteogenesis and angiogenesis may provide better outcomes for early stage disease. In this study, genetically engineered bone-marrow stem cells were used to enhance repair of a defect in the distal aspect of the femur.
Cloned bone-marrow stem cells were transfected with traceable genes. Osteoblastic and angiogenic properties of the cells were analyzed. A defect was created bilaterally in the distal portion of the femur of twenty-four mice to mimic a core decompression procedure. The cloned cells were transplanted into each defect of the right femur while the left femur served as control. Bone formation was evaluated radiographically and histomorphometrically. In addition, in twenty-four additional mice, the cells were injected into subcutaneous sites, muscles, and into the renal capsule (eight mice in each group) to evaluate ectopic osteogenesis.
Radiopaque tissue appeared two weeks after the cells were transplanted into bone defects and at ectopic sites. Histologic analysis demonstrated that these tissues consisted of newly formed bone from transplanted cells that expressed traceable genes. Four of six bone defects that received cell transplantation were filled with new bone at four weeks, and all of the defects (n = 6) demonstrated complete healing at six weeks. On the control side, complete repair was seen in only two of six bone defects at four weeks and in three of six defects at six weeks. Histomorphometric analysis showed that transplantation of marrow stem cells into bone defects produced more bone at an earlier time-point than occurred in the controls.
This study demonstrated that cloned bone-marrow stem cells can directly form bone after transplantation into bone defects and at ectopic sites, indicating that the in vitro expanded bone-marrow stem cells can serve as a graft material to enhance bone repair and to treat osteonecrosis.
As an alternative graft material, bone-marrow stem cells may provide new and as yet technologically unachievable solutions to many clinical problems in the areas of musculoskeletal reconstruction and tissue regeneration.
骨坏死的治疗仍然是一个具有挑战性的问题。用促进骨生成和血管生成的移植材料替代坏死骨可能为早期疾病提供更好的治疗效果。在本研究中，使用基因工程骨髓干细胞来增强股骨远端缺损的修复。
用可追踪基因转染克隆的骨髓干细胞。分析细胞的成骨和血管生成特性。在24只小鼠的股骨远端双侧制造缺损以模拟髓芯减压手术。将克隆细胞移植到右股骨的每个缺损处，而左股骨作为对照。通过放射学和组织形态计量学评估骨形成。此外，在另外24只小鼠中，将细胞注射到皮下部位、肌肉和肾包膜中（每组8只小鼠）以评估异位骨生成。
将细胞移植到骨缺损和异位部位两周后出现不透射线的组织。组织学分析表明，这些组织由表达可追踪基因的移植细胞形成的新骨组成。接受细胞移植的6个骨缺损中有4个在4周时被新骨填充，所有缺损（n = 6）在6周时显示完全愈合。在对照侧，6个骨缺损中只有2个在4周时完全修复，6个缺损中有3个在6周时完全修复。组织形态计量学分析表明，将骨髓干细胞移植到骨缺损中比对照组在更早的时间点产生更多的骨。
本研究表明，克隆的骨髓干细胞移植到骨缺损和异位部位后可直接形成骨，表明体外扩增的骨髓干细胞可作为移植材料增强骨修复并治疗骨坏死。
作为一种替代移植材料，骨髓干细胞可能为肌肉骨骼重建和组织再生领域的许多临床问题提供新的、目前技术上无法实现的解决方案。
