The Journal of Bone and Joint Surgery (American). 2006;88:167-172.
doi:10.2106/JBJS.F.00891
© 2006 The Journal of Bone and Joint Surgery, Inc.
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Use of Genetically Engineered Bone-Marrow Stem Cells to Treat Femoral Defects: An Experimental Study

Quanjun Cui, MD, Zengming Xiao, MD, Xudong Li, MD, PhD, Khaled J. Saleh, MD, MSc, FRCSC and Gary Balian, PhD

Corresponding author:
Quanjun Cui, MD
Department of Orthopaedic Surgery, Orthopaedic Research Laboratories, University of Virginia School of Medicine, Box 800159, Charlottesville, VA 22908.
E-mail address for Q. Cui: qc4q{at}hscmail.mcc.virginia.edu

The authors did not receive grants or outside funding in support of their research for or preparation of this manuscript. They did not receive payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, educational institution, or other charitable or nonprofit organization with which the authors are affiliated or associated.

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Clinical Relevance: 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.


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