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Evidence for Skeletal Progenitor Cells in the Degenerate Human Intervertebral Disc

Risbud, Makarand V., PhD*; Guttapalli, Asha, MS*; Tsai, Tsung-Ting, MD*†; Lee, Joon Y., MD*‡; Danielson, Keith G., PhD*; Vaccaro, Alexander R., MD*; Albert, Todd J., MD*; Gazit, Zulma, PhD§; Gazit, Dan, PhD§; Shapiro, Irving M., PhD*

doi: 10.1097/BRS.0b013e318158dea6
Basic Science
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SDC

Study Design. To identify and characterize endogenous progenitor cell population from intervertebral disc.

Objective. To determine if progenitor cells exist in degenerate human discs.

Summary of Background Data. Back pain, a significant source of morbidity in our society, is directly linked to the pathology of the intervertebral disc. Because disc disease is accompanied by a loss of cellularity, there is considerable interest in regeneration of cells of both the anulus fibrosus (AF) and nucleus pulposus (NP).

Methods. To determine if skeletal progenitor cells are present in the disc, samples were obtained from the degenerate AF and NP of 5 patients (Thompson grade 2 and 3, mean age 34 ± 7.6 years) undergoing anterior cervical discectomy and fusion procedures as well as adult rat lumbar spine.

Results. Cells isolated from degenerate human tissues expressed CD105, CD166, CD63, CD49a, CD90, CD73, p75 low affinity nerve growth factor receptor, and CD133/1, proteins that are characteristic of marrow mesenchymal stem cells. In osteogenic media, there was an induction of alkaline phosphatase activity and expression of alkaline phosphatase, osteocalcin, and Runx-2 mRNA. When maintained in adipogenic media, a small percentage of cells displayed evidence of adipogenic differentiation: accumulation of cytosolic lipid droplets and increased expression of peroxisome proliferator-activated receptor-γ2 and lipoporotein lipase mRNA. AF- and NP-derived cells also evidenced chondrogenic differentiation. CD133 (+) cells in the AF were able to commit to either the chondrogenic or adipogenic lineages. The results of the human disc studies were confirmed using cell derived from the NP and AF tissue of the mature rat disc.

Conclusion. The analytical data indicated that the pathologically degenerate human disc contained populations of skeletal progenitor cells. These findings suggest that these endogenous progenitors may be used to orchestrate the repair of the intervertebral disc.

The aim of the study was to elucidate if skeletal progenitor cells exist in degenerate human discs. Results of the study show that a small proportion of cells from degenerate human and normal rat discal tissues commit to different mesenchymal lineages. These findings suggest that these progenitors may be used to orchestrate the repair of the disc.

From the *Department of Orthopaedic Surgery and Graduate Program in Tissue Engineering and Regenerative Medicine, Thomas Jefferson University, Philadelphia, PA; †Department of Orthopaedic Surgery, Chang-Gung Memorial Hospital, Chang Gung University, Taipei, Taiwan, Republic of China; ‡Department of Orthopaedics, Spine Surgery Division, University of Pittsburgh Medical Center, Pittsburgh, PA; and §Skeletal Biotechnology Laboratory, The Hebrew University of Jerusalem—Hadassah Medical and Gene Therapy Center, Jerusalem, Israel and the International Stem Cell Institute, Department of Surgery, Cedar Sinai Medical Center, Los Angeles, CA.

Acknowledgment date: February 13, 2007. Revision date: May 15, 2007. Acceptance date: May 16, 2007.

The manuscript submitted does not contain information about medical device(s)/drug(s).

Federal funds were received in support of this work. No benefits in any form have been or will be received from a commercial party related directly or indirectly to the subject of this manuscript.

This study was funded by NIH AR050087.

Address correspondence and reprint requests to Makarand V. Risbud, PhD, Department of Orthopaedic Surgery, 1015 Walnut Street, Suite 5, 01 Curtis Bldg., Thomas Jefferson University, Philadelphia, PA 19107; E-mail: makarand.risbud@jefferson.edu

© 2007 Lippincott Williams & Wilkins, Inc.