Genetically Modified Human Derived Bone Marrow Cells for Posterolateral Lumbar Spine Fusion in Athymic Rats

Abstract

This study demonstrates that human-derived bone marrow cells can be infected with a BMP-2-containing adenovirus and produce sufficient bone in vivo to fuse the lumbar spine.

Regional gene therapy to enhance bone repair

“…These same investigators have also transduced human bone marrow cells with an adenovirus containing the cDNA for BMP-2 and were able to induce fusion of the spines in nude rats. 34 These studies with human cells demonstrate proof of the concept that human cells can be genetically manipulated to overexpress osteoinductive proteins and enhance bone repair.…”

“…Human cells have now been used to heal critical-sized defects and induce spinal fusion in animal models. 30,34 However, gene therapy should be viewed as only one aspect of a more comprehensive tissue engineering approach to treating bone repair problems in patients. Autologous bone graft, cell-based therapy and recombinant proteins will be used to treat a variety of bone loss proteins.…”

Ex Vivo Gene Therapy for Spinal Fusion

“…The researchers concluded that ex vivo AdBMP-2 transduction produced solid posterolateral spinal fusion in rats and was superior to ICBG alone (Wang et al, 2003). The same group also reported that human bone marrow cells can be infected by AdBMP-2 and produce sufficient bone in vivo to fuse the lumbar spine in athymic rats (Peterson et al 2005). Miyazaki et al have compared lentiviral and adenoviral gene therapy.…”

An update on bone substitutes for spinal fusion

“…At 8 weeks postinjection, CT scans and histological analysis clearly demonstrated large volumes of ectopic bone at the injection sites, resulting in successful spinal fusion [30]. Moreover, Peterson et al [70] performed posterolateral fusion surgically using human-derived bone marrow cells transfected with Ad-BMP-2 in athymic nude rats and demonstrated sufficient spinal fusions.…”

“…Various improvements have been implemented to ensure such safety [82,97,114], and gene therapy has been validated as a safe technique in preclinical animal experiments [13,30,43,64,70,99,101]. However, long-term results have not yet been elucidated, and further studies are required before these vectors can be used in clinical practice.…”