Research article summary (published 13 Apr 2008):

Cell therapy using articular chondrocytes overexpressing BMP-7 or BMP-10 in a rabbit disc organ culture model.

Full Abstract

STUDY DESIGN: Rabbit knee articular chondrocytes overexpressing human growth factors were injected into cultured intervertebral disc explants. Survival of the injected cells and accumulation of extracellular matrix were assessed. OBJECTIVE: To define the utility of cell-based gene delivery approach for repair of the intervertebral disc. SUMMARY OF BACKGROUND DATA: Back pain associated with symptomatic disc degeneration is a common clinical condition. Growth factors stimulate disc cell metabolism, but the ideal method for in vivo delivery has not been established. Cells as a vehicle for delivering growth factors to the disc offer potential advantages, including prolonged production of the growth factor within the disc and vital cells to participate in the repair process. METHODS: New Zealand white rabbit articular chondrocytes transduced with adenovirus expressing human bone morphogenetic protein-7 and green fluorescence protein (GFP) (AdhBMP-7), human bone morphogenetic protein-10 and GFP (AdBMP-10), or GFP alone (AdGFP, as a control) were injected into whole disc explants. Discs were maintained in culture for 1 to 2 months. At the conclusion of the culture periods, cell survival was assessed by fluorescence microscopy and extracellular matrix accumulation was assessed with biochemical methods. RESULTS: Chondrocytes achieved long-term survival in the cultured disc explants. The discs treated with chondrocytes/BMP-7 demonstrated a 50% increase in proteoglycan content within the nucleus pulposus compared to control (chondrocytes/GFP), while discs injected with chondrocytes/BMP-10 failed to show a significant increase in proteoglycan accumulation. CONCLUSION: Our study demonstrates the ability of transduced articular chondrocytes to survive and promote proteoglycan accumulation when transplanted into the intervertebral disc. These data support the potential of a cell-based gene therapy approach for disc repair. Further studies using this approach in animal models are indicated as a step towards achieving disc repair in humans.

Author information

Author/s: Zhang, Yejia (Y); Phillips, Frank M (FM); Thonar, Eugene J-M A (EJ); Oegema, Theodore (T); An, Howard S (HS); Roman-Blas, Jorge A (JA); He, Tong-Chuan (TC); Anderson, D Greg (DG);

Affiliation: Departments of Rehabilitation Medicine, Thomas Jefferson University, Philadelphia, PA 19107, USA. Yejia.Zhang(-atsign-)jefferson.edu

Grants: 1K08 HD049598-01 (Agency:NICHD NIH HHS) ; 2K12 HD0197-7 (Agency:NICHD NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

Journal: Spine (Spine (Phila Pa 1976)), published in United States. (Language: eng)

Reference: 2008-Apr; vol 33 (issue 8) : pp 831-8

Dates: Created 2008/04/11; Completed 2008/05/15; Revised 2009/07/09;

PMID: 18404100, status: MEDLINE (last retrieval date: 7/24/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Adenoviridae - genetics Animals Bone Morphogenetic Protein 7 Bone Morphogenetic Proteins - biosynthesis; genetics Cartilage, Articular - cytology Cell Survival Cell Transplantation Chondrocytes - cytology; metabolism; transplantation Extracellular Matrix - metabolism Female

Gene Expression Intervertebral Disk - cytology; metabolism Joints - cytology Male Organ Culture Techniques RNA, Messenger - metabolism Rabbits Reverse Transcriptase Polymerase Chain Reaction Transduction, Genetic - methods Transforming Growth Factor beta - biosynthesis; genetics

Associated Chemicals: BMP7 protein, human (0) ; Bone Morphogenetic Protein 7 (0) ; Bone Morphogenetic Proteins (0) ; RNA, Messenger (0) ; Transforming Growth Factor beta (0)

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