Inducing Angiogenesis in the Nucleus Pulposus.

Area of Science:

• Spinal fusion research
• Regenerative medicine
• Tissue engineering

Background:

• Bone morphogenetic protein (BMP) gene delivery to intervertebral discs (IVDs) typically induces bone formation outside the disc.
• The IVD microenvironment is considered unfavorable for osteogenesis and vascularization.
• Strategies to enhance intra-discal bone formation and fusion are needed.

Purpose of the Study:

• To investigate if IVD matrix degradation and enhanced vascularization can promote intra-discal osteogenesis and spinal fusion.
• To evaluate the effects of chondroitinase-ABC (chABC) and vascular endothelial growth factor (VEGF) on BMP-driven osteogenesis within the IVD.

Main Methods:

• Lewis rats underwent surgical intra-discal delivery of gene-modified cells (BMP2/BMP7 or VEGF165) with or without chABC.
• Radiographic, histological, and biomechanical analyses were performed to assess bone formation and fusion.
• Western blotting was used to analyze soluble Flt1 (sFlt) levels.

Main Results:

• BMP and VEGF/BMP treatments resulted in increased stiffness, bone production, and fusion, but bone formation was external to the IVD.
• chABC treatment impaired BMP-driven osteogenesis, reduced proteoglycans, and promoted IVD angiogenesis.
• chABC treatment liberated soluble Flt1 from the IVD matrix, suggesting a mechanism for angiogenesis.

Conclusions:

• The IVD microenvironment can be manipulated to facilitate vascular invasion.
• While intra-discal osteogenesis was not achieved, these findings suggest potential pathways for enhancing spinal fusion therapies.