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Enhanced Meniscal Repair by Overexpression of hIGF-1 in a Full-thickness Model

  • Symposium: Tribute to Dr. Marshall Urist: Musculoskeletal Growth Factors
  • Published:
Clinical Orthopaedics and Related Research®

Abstract

The importance of the menisci to the well-being of the normal knee is well-documented. However, there is no ideal repair or reconstructive approach for damaged menisci. Gene therapy provides one promising alternative strategy, especially when combined with injectable tissue engineering to achieve minimally invasive clinical application. We asked whether the introduction of human insulin-like growth factor 1 (hIGF-1) gene could improve the repair of full-thickness meniscal defects. We created full-thickness meniscal defects in the “white area” of the anterior horn in 48 goats. Bone marrow stromal cells with the transfection of hIGF-1 gene and injectable calcium alginate gel were mixed together to repair the defects; three control groups included cells without transfection, gel without cells, and defects left empty. After 4, 8, and 16 weeks, the animals were euthanized and the excised defects were examined by macroscopic assessment, histological analysis, electron microscopy, proteoglycan determination, and MRI. Sixteen weeks after surgery the repaired meniscal defects were filled with white tissue similar to that in normal meniscal fibrocartilage. The repair tissue was composed of cells embedded within matrix that filled the spaces of the fibers. The proteoglycan content in the gene-enhanced tissue engineering group was higher than those in the control groups, and less than that in the normal meniscus. The results suggest full-thickness meniscal defects in regions without blood supply can be reconstructed with hIGF-1-enhanced injectable tissue engineering.

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Acknowledgments

We thank Dr Xiaokui Hou and Dr Yingzhen Wang for assistance with the manuscript. We also thank Dr Guanzhen Yang and Dr Xiangfu Wu for their technical assistance on molecular technology and Dr Chengyu Lv, Dr Xiaoming Xing, and Dr Wenjian Xu for their help with the histologic and imageologic analysis. We thank Hao Xu for his assistance on statistical analysis.

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Correspondence to Haining Zhang PhD, MD.

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Two of the authors (HZ, PL) received funding from the National Natural Science Foundation of China (No 30801167).

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.

Each author certifies that his or her institution has approved the animal protocol for this investigation and that all investigations were conducted in conformity with ethical principles of research.

This work was performed at Department of Joint Surgery, The Affiliated Hospital of Tsingtao University, Tsingtao, China.

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Zhang, H., Leng, P. & Zhang, J. Enhanced Meniscal Repair by Overexpression of hIGF-1 in a Full-thickness Model. Clin Orthop Relat Res 467, 3165–3174 (2009). https://doi.org/10.1007/s11999-009-0921-8

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  • DOI: https://doi.org/10.1007/s11999-009-0921-8

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