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


BACKGROUND
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.


CONCLUSIONS
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.
Zhang
Yejia
Y
Departments of Rehabilitation Medicine, Thomas Jefferson University, Philadelphia, PA 19107, USA. Yejia.Zhang@jefferson.edu
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
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000096:biosynthesis* / Q000235:genetics; D002358:Cartilage, Articular / Q000166:cytology*; D002470:Cell Survival; D017690:Cell Transplantation; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D007403:Intervertebral Disc / Q000166:cytology* / Q000378:metabolism; D007596:Joints / Q000166:cytology; D008297:Male; D009924:Organ Culture Techniques; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014161:Transduction, Genetic / Q000379:methods*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics
C525819:BMP7 protein, human; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta