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.
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 humanbone morphogenetic protein-7 and green fluorescence protein (GFP) (AdhBMP-7), humanbone 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.
Authors: Yejia Zhang; Ana Chee; Peng Shi; Rui Wang; Isaac Moss; Er-Yun Chen; Tong-Chuan He; Howard S An Journal: Am J Phys Med Rehabil Date: 2015-07 Impact factor: 2.159
Authors: Khoi D Than; Shayan U Rahman; Lin Wang; Adam Khan; Kwaku A Kyere; Tracey T Than; Yoshinari Miyata; Yoon-Shin Park; Frank La Marca; Hyungjin M Kim; Huina Zhang; Paul Park; Chia-Ying Lin Journal: Spine J Date: 2013-12-01 Impact factor: 4.166
Authors: D Greg Anderson; Dessislava Markova; Howard S An; Ana Chee; Motomi Enomoto-Iwamoto; Vladimir Markov; Biagio Saitta; Peng Shi; Chander Gupta; Yejia Zhang Journal: Am J Phys Med Rehabil Date: 2013-05 Impact factor: 2.159
Authors: Nicole Willems; Frances C Bach; Saskia G M Plomp; Mattie H P van Rijen; Jeannette Wolfswinkel; Guy C M Grinwis; Clemens Bos; Gustav J Strijkers; Wouter J A Dhert; Björn P Meij; Laura B Creemers; Marianna A Tryfonidou Journal: Arthritis Res Ther Date: 2015-05-27 Impact factor: 5.156