#51 Intervertebral Disc Repair and Regeneration Using Neonatal Human Dermal Fibroblasts in the Rabbit Model

General Session: Best Papers Session

Presented by: H. An

Author(s):

A. Chee (1)
P. Shi (1)
T.D. Cha (2)
T.-H. Kao (3)
S.-H. Yang (4)
Y. Zhang (1)
H.S. An (1)

(1) Rush University Medical Center, Chicago, IL, USA
(2) Massachusetts General Hospital, Boston, MA, USA
(3) Taichung Veterans General Hospital, Taichung, Taiwan, Republic of China
(4) National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan, Republic of China

Abstract

Background Context: Low back pain is the primary cause of disability in individuals under the age of 45 and presents a major burden on the medical, social, and economic structures of all developed countries. The success rates of reducing back pain using current procedures such as steroid injection, pain medication, physical therapy and surgery are often unpredictable. As research breakthroughs improve our understanding of the biology of the spine, new biological therapies are being developed to help regenerate the spinal tissues and restore function. Cell therapy using human dermal fibroblasts includes injection of cells from the patient's skin tissue or from a donor tissue into the spine where the cells can replicate and regenerate tissues. Human dermal fibroblast cell therapy may be most beneficial when disc degeneration is severe and a large number of the patient´s own disc cells are already dead.

Purpose: To determine the effects of intradiscal transplantation of neonatal human dermal fibroblast cells (nHDFs) on the progression of intervertebral disc (IVD) degeneration by measuring radiographic, magnetic resonance imaging (MRI), biochemical, histological, and gene expression changes.

Study Design: This in vivo study was conducted in the established rabbit disc injury model to determine the effects of injecting nHDFs in degenerating intervertebral discs.

Methods: New Zealand white rabbits (n=16) received an annular puncture using an 18-guage needle to induced disc degeneration at levels: L1/2, L2/3, L4/5 and L5/6. Four weeks after injury, the rabbits were randomized and the IVDs subjected to treatment with infrared dye-labeled nHDFs or saline. At two and eight weeks post-injection, animals were sacrificed; spines and IVDs were isolated and imaged with the infrared imager to determine presence of transplanted nHDFs. RNA from the IVDs was then analyzed for expression of phenotypic IVD marker genes. At eight weeks post-injection, X-ray images were obtained to determine disc height indices. The animals were sacrificed and the spines were further imaged using T2 weighted MRI and infrared imaging. After the imaging studies, IVDs were isolated for histological features and biochemical changes. The outcome measures were compared between the intradiscal nHDF treatment group and the control group.

Results: The infrared imaging studies showed that nHDFs were retained in the disc at the same level of infrared intensity at both 2 and 8 weeks after transplantation. Collagen type II gene expression, a marker for disc repair and regeneration, was higher in the discs treated with nHDFs than those in the control saline treatment. Also higher in the cell treated discs were the disc heights and cell number.

Conclusions: Together, this data suggests that human dermal fibroblast cells are a promising option for cell therapy that may restore the biological function and reduce symptoms of intermediate or progressive degenerative discs. More studies will be needed before this therapy would be a viable treatment option for patients with low back pain.