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Acta Biomater. 2019 Mar 15;87:118-129. doi: 10.1016/j.actbio.2019.01.050. Epub 2019 Jan 25.

Intervertebral disc regeneration with an adipose mesenchymal stem cell-derived tissue-engineered construct in a rat nucleotomy model.

Author information

1
Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
2
Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. Electronic address: takashikaito@ort.med.osaka-u.ac.jp.
3
Division of Intelligent Mechanical Systems, Faculty of System Design, Tokyo Metropolitan University, 6-6, Asahigaoka, Hino, Tokyo 191-0065, Japan.
4
Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan; Sensory & Motor System Medicine, The University of Tokyo Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8654, Japan.
5
Department of Orthopaedic Surgery, National Hospital Organization, Osaka Minami Medical Center, 2-1 Kidohigashi, Kawachinagano, Osaka 586-8521, Japan.
6
Department of Orthopaedics, University of Maryland School of Medicine, 655 W. Baltimore Street, Baltimore, MD 21201, USA.
7
McCaig Institute for Bone & Joint Health, Cumming School of Medicine, University of Calgary, 3280 Hospital Drive NW, Calgary, AB T2N 4Z6, Canada.
8
Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan; Institute for Medical Science in Sports, Osaka Health Science University, 1-9-27, Tennma, Kita-ku, Osaka 530-0043, Japan; Center for Advanced Medical Engineering and Informatics, Osaka University, 2-2 Yamadaoka, Suita City, Osaka 565-0871, Japan.

Abstract

Low back pain results in more global disabilities than any other condition, and intervertebral disc (IVD) degeneration is commonly involved in the etiology. Supplementation of IVDs with reparative cells is a rational strategy to address such clinical problems. We have previously developed a scaffold-free tissue-engineered construct (TEC) as a novel cell therapy system for repair of articular cartilage and meniscus. We now show the regenerative potential of adipose mesenchymal stem cells derived TEC (ADSC-TEC) for IVD degeneration using a rat tail model of total nucleotomy. The regenerative efficacy of ASDC-TEC was investigated structurally and biomechanically up to 6 months after implantation. ADSC-TEC implantation into IVDs preserved the disc height, endplate, and annulus fibrosus structure, and showed similar biomechanical characteristics to the sham group at postoperative 6 weeks. The structure of regenerated IVD was maintained until 6 months. Furthermore, ADSC-TEC implantation attenuated the impact of age-related biomechanical deterioration when assessed at 6 months post-implantation. These results demonstrate that use of ADSC-TECs can be an effective treatment for IVD degeneration. STATEMENT OF SIGNIFICANCE: We developed adipose mesenchymal stem cell-derived scaffold-free tissue engineered construct (ADSC-TEC) as a novel cell therapy system. The ADSC-TEC implantation into a rat total-nucleotomized disc space regenerated intervertebral discs (IVDs) histologically and biomechanically. The regenerative capacity of the ADSC-TEC was exerted by its trophic effects on annulus fibrosus cells and the load-sharing effect at intervertebral space. Interestingly, the regenerated IVDs by the ADSC-TEC was less susceptible to the age-related deterioration than the IVDs of normal rats. Thus, the application of ADSC-TEC into the degenerated disc can be an alternative therapy for various disease associated with structural and functional failure of IVDs.

KEYWORDS:

Biomaterials; Intervertebral disc; Mesenchymal stem cells; Regeneration; Total nucleotomy

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