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Emerging Ideas: Treatment of Precollapse Osteonecrosis Using Stem Cells and Growth Factors

  • Emerging Ideas
  • Published:
Clinical Orthopaedics and Related Research®

Abstract

Background

Osteonecrosis (ON) of the femoral head is a devastating disease affecting young patients at their most productive age, causing major socioeconomic burdens. ON is associated with various etiologic factors, and the pathogenesis of the disease is unknown. Most investigators believe the disease is the result of secondary microvascular compromise with subsequent bone and marrow cell death and defective bone repair.

Questions/Hypotheses

We hypothesize that local delivery of vascular endothelial growth factor (VEGF) and bone morphogenetic protein-6 (BMP-6), which induces angiogenesis and osteogenesis respectively, will reverse the disease process and provide a treatment for precollapse ON.

Method of Study

We will use genetically engineered bone marrow stem cells, carrying VEGF and BMP-6 genes, to enhance angiogenesis and osteogenesis in necrotic bone of an animal model, by local delivery of growth factor in addition to the bone-forming property of the stem cells. The participation, localization, and fate of the stem cells in the repair process will be evaluated by tracing marker-gene product. Osteogenesis and angiogenesis will be assessed using high-resolution xray CT and immunohistomorphometry quantitatively. Mechanical properties of the repair tissue will be determined using an indentation test of the femoral head.

Significance

We envision that a deliverable or injectable bone graft substitute containing engineered stem cells and therapeutic growth factors will be developed through this proposed study and will provide a much needed treatment for ON.

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Acknowledgments

We thank Drs. Regis J. O’Keefe and Roy K. Aaron for their mentorship and OREF, ORS, and AAOS for organizing the Grant Writing Workshop.

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Authors and Affiliations

  1. Department of Orthopaedic Surgery, Orthopaedic Trauma Service, University of Virginia School of Medicine, P.O. Box 800159, Charlottesville, VA, 22908, USA

    Quanjun Cui MD, MSc & Edward A. Botchwey PhD

  2. Department of Biomedical Engineering (BME), University of Virginia School of Medicine, Charlottesville, VA, USA

    Edward A. Botchwey PhD

Authors
  1. Quanjun Cui MD, MSc
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  2. Edward A. Botchwey PhD
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Corresponding author

Correspondence to Quanjun Cui MD, MSc.

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Each author certifies that he or she has no commercial associations (eg, consultancies, stock ownership, equity interest, patent/licensing arrangements, etc) that might pose a conflict of interest in connection with the submitted article.

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Cui, Q., Botchwey, E.A. Emerging Ideas: Treatment of Precollapse Osteonecrosis Using Stem Cells and Growth Factors. Clin Orthop Relat Res 469, 2665–2669 (2011). https://doi.org/10.1007/s11999-010-1738-1

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  • DOI: https://doi.org/10.1007/s11999-010-1738-1

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