Lumbar Spine Intervertebral Disc Gene Delivery: A Pilot Study in Lewis Rats

Sheela R. Damle BS,
Hospital for Special Surgery, New York, NY

Bernard A. Rawlins, MD
Attending Orthopaedic Surgeon, Hospital for Special Surgery
Professor of Clinical Orthopaedic Surgery, Weill Cornell Medical College

Oheneba Boachie-Adjei, MD
Chief of Scoliosis Service, Hospital for Special Surgery
Attending Orthopedic Surgeon, Hospital for Special Surgery
Professor of Orthopedic Surgery, Weill Cornell Medical College

Ronald G. Crystal MD,
Department of Genetic Medicine and Belfer, Gene Therapy Core Facility, Weill Cornell Medical College, New York, NY

Chisa Hidaka MD
Department of Genetic Medicine and Belfer, Gene Therapy Core Facility, Weill Cornell Medical College, New York, NY


Matthew E. Cunningham, MD, PhD

Matthew E. Cunningham, MD, PhD

Assistant Attending Orthopaedic Surgeon, Hospital for Special Surgery
Assistant Professor in Orthopaedic Surgery, Weill Cornell Medical College

Abstract

Background

Basic research toward understanding and treating disc pathology in the spine has utilized numerous animal models, with delivery of small molecules, purified factors, and genes of interest. To date, gene delivery to the rat lumbar spine has only been described utilizing genetically programmed cells in a matrix which has required partial disc excision, and expected limitation of treatment diffusion into the disc.

Purpose

This study was designed to develop and describe a surgical technique for lumbar spine exposure and disc space preparation, and use of a matrix-free method for gene delivery.

Methods

Naïve or genetically programmed isogeneic bone marrow stromal cells were surgically delivered to adolescent male Lewis rat lumbar discs, and utilizing quantitative biochemical and qualitative immunohistological assessments, the implanted cells were detected 3 days post-procedure.

Results

Statistically significant differences were noted for recovery of the -galactosidase marker gene comparing delivery of naïve or labeled cells (105 cells per disc) from the site of implantation, and between delivery of 105 or 106 labeled cells per disc at the site of implantation and the adjacent vertebral body. Immunohistology confirmed that the -galactosidase marker was detected in the adjacent vertebra bone in the zone of surgical implantation.

Conclusions

The model requires further testing in larger cohorts and with biologically active genes of interest, but the observations from the pilot experiments are very encouraging that this will be a useful comparative model for basic spine research involving gene or cell delivery, or other locally delivered therapies to the intervertebral disc or adjacent vertebral bodies in rats.

This article appears in HSS Journal: Volume 9, Number 1.
View the full article at springerlink.com.

About the HSS Journal

HSS Journal, an academic peer-reviewed journal published three times a year, February, July and October. The Journal accepts and publishes peer reviewed articles from around the world that contribute to the advancement of the knowledge of musculoskeletal diseases and disorders.

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