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

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.

journal_name

Spine (Phila Pa 1976)

journal_title

Spine

authors

Zhang Y,Phillips FM,Thonar EJ,Oegema T,An HS,Roman-Blas JA,He TC,Anderson DG

doi

10.1097/BRS.0b013e31816b1f38

subject

Has Abstract

pub_date

2008-04-15 00:00:00

pages

831-8

issue

eissn

0362-2436

issn

1528-1159

pii

00007632-200804150-00002

journal_volume

pub_type

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