16
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Cell Therapy with Human Dermal Fibroblasts Enhances Intervertebral Disk Repair and Decreases Inflammation in the Rabbit Model

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Study Design Pilot study using the rabbit model.

          Objective Low back pain is often associated with disk degeneration. Cell therapy for degenerating disks may promote tissue regeneration and repair. Human dermal fibroblasts, obtained from the patient's skin tissue or donated tissue, may be a promising cell therapy option for degenerating disks. The objective of these studies is to determine the effects of intradiscal transplantation of neonatal human dermal fibroblasts (nHDFs) on intervertebral disk (IVD) degeneration by measuring disk height, magnetic resonance imaging (MRI) signal intensity, gene expression, and collagen immunostaining.

          Methods New Zealand white rabbits ( n = 16) received an annular puncture to induce disk degeneration and were treated with nHDFs or saline 4 weeks later. At 2 and 8 weeks post-treatment, X-ray and MRI images were obtained. IVDs were isolated and examined for changes in collagen staining and gene expression.

          Results In the nHDF-treated group, there was a 10% increase in the disk height index after 8 weeks of treatment ( p ≤ 0.05), and there was no significant difference in the saline-treated group. When compared with the saline-treated disks, disks treated with nHDFs showed reduced expression of inflammatory markers, a higher ratio of collagen type II over collagen type I gene expression, and more intense immunohistochemical staining for both collagen types I and II.

          Conclusions Human dermal fibroblast introduction into the disk reduced inflammation and promoted tissue rich in both type I and type II collagens. The results of this study suggest that nHDFs would be a feasible cell therapy option for disk degeneration.

          Related collections

          Most cited references27

          • Record: found
          • Abstract: found
          • Article: not found

          A novel rabbit model of mild, reproducible disc degeneration by an anulus needle puncture: correlation between the degree of disc injury and radiological and histological appearances of disc degeneration.

          An in vivo study to radiographically and histologically assess a new method of induction of disc degeneration. OBJECTIVE.: To establish a reproducible rabbit model of disc degeneration by puncturing the anulus with needles of defined gauges and to compare it to the classic stab model. New treatment approaches to disc degeneration are of great interest. Although animal models for disc degenerative disease exist, the quantitative measurement of disease progression remains difficult. A reproducible, progressive disc degeneration model, which can be induced in a reasonable time frame, is essential for development of new therapeutic interventions. The classic anular stab model and the new needle puncture model were used in the rabbit. For the needle puncture model, 3 different gauges of needle (16G, 18G, and 21G) were used to induce an injury to the disc to a depth of 5 mm. Radiographic and histologic analyses were performed; magnetic resonance images were also assessed in the needle puncture model. Significant disc space narrowing was observed as early as 2 weeks after stabbing in the classic stab model; there was no further narrowing of the disc space. In the needle puncture model, all needle sizes tested induced a slower and more progressive decrease in disc height than in the classic stab model. The magnetic resonance imaging supported the results of disc height data. The needle puncture approach, using 16G to 21G needles, resulted in a reproducible decrease of disc height and magnetic resonance imaging grade. The ease of the procedure and transfer of the methodology will benefit researchers studying disc degeneration.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Intervertebral discs which cause low back pain secrete high levels of proinflammatory mediators.

            Herniated intervertebral disc tissue has been shown to produce a number of proinflammatory mediators and cytokines, but there have been no similar studies using discs from patients with discogenic low back pain. We have compared the levels of production of interleukin-6 (IL-6), interleukin-8 (IL-8) and prostaglandin E2 (PGE2) in disc tissue from patients undergoing discectomy for sciatica (63) with that from patients undergoing fusion for discogenic low back pain (20) using an enzyme-linked immunoabsorbent assay. There was a statistically significant difference between levels of production of IL-6 and IL-8 in the sciatica and low back pain groups (p < 0.006 and p < 0.003, respectively). The high levels of proinflammatory mediator found in disc tissue from patients undergoing fusion suggest that production of proinflammatory mediators within the nucleus pulposus may be a major factor in the genesis of a painful lumbar disc.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Clinical experience in cell-based therapeutics: disc chondrocyte transplantation A treatment for degenerated or damaged intervertebral disc.

              Disc herniation treated by discectomy results in a significant loss of nucleus material and disc height. Biological restoration through the use of autologous disc chondrocyte transplantation offers a potential to achieve functional integration of disc metabolism and mechanics. Chondrocytes that have been removed from damaged cartilaginous tissues maintain a capacity to proliferate, produce and secrete matrix components and respond to physical stimuli such as dynamic loading. Nucleus regeneration using autologous cultured disc-derived chondrocytes (ADCT) has been demonstrated in a canine model and in clinical pilot studies. In 2002 a prospective, controlled, randomised, multi-center study, EuroDISC, comparing safety and efficacy of autologous disc chondrocyte transplant, chondrotransplant DISC, plus discectomy (ADCT), with discectomy alone was initiated. A dog model was used to investigate the hypothesis that autologous disc chondrocytes can be used to repair damaged intervertebral disc. Disc chondrocytes were harvested and expanded in culture under controlled and defined conditions, returned to the same animals from which they had been sampled (autologous transplantation) via percutaneous delivery. The animals were analyzed at specific times after transplantation by several methods to examine whether disc chondrocytes integrated with the surrounding tissue, produced the appropriate intervertebral disc extracellular matrix, and might provide a formative solution to disc repair. The clinical goals of the EuroDISC study, were to provide long-term pain relief, maintain disc height and prevent adjacent segment disease. Interim analysis was performed after 2 years; Oswestry (low back pain/disability), Quebec Back-Pain Disability Scale, as well as Prolo and VAS score were used for the evaluation. Disc height was assessed by MRI. In the context of degenerative changes in an injury model: () autologous disc chondrocytes were expended in culture and returned to the disc by a minimally invasive procedure after 12 weeks; () disc chondrocytes remained viable after transplantation as shown by bromodeoxyuridine incorporation and maintained a capacity for proliferation after transplantation as depicted by histology; () transplanted disc chondrocytes produced an extracellular matrix that displayed composition similar to normal intervertebral disc tissue. Positive evidence of Proteoglycan content was supported by accepted histochemical staining techniques such as Safranin O-Fast Green; () both Type II and Type I collagens were demonstrated in the regenerated intervertebral disc matrix by immunohistochemistry after chondrocyte transplantation; and () when the disc heights were analyzed for variance according to treatment a statistically significant-correlation between transplanting cells and retention of disc height was achieved. A clinically significant reduction of low back pain in the ADCT-treated group was shown by all three pain score systems. The median total Oswestry score was 2 in the ADCT-treated group compared with 6 in the control group. Decreases in the disability index and VAS score in ADCT-treated patients correlated strongly with the reduction of low back pain. Decreases in disc height over time were only found in the control group, and of potential significance, intervertebral discs in adjacent segments appeared to retain hydration when compared to those adjacent to levels that had undergone discectomy without cell intervention. Autologous chondrocyte transplantation is technically feasible and biologically relevant to repairing disc damage and retarding disc degeneration.
                Bookmark

                Author and article information

                Journal
                Global Spine J
                Global Spine J
                10.1055/s-00000177
                Global Spine Journal
                Georg Thieme Verlag KG (Stuttgart · New York )
                2192-5682
                2192-5690
                13 April 2016
                December 2016
                : 6
                : 8
                : 771-779
                Affiliations
                [1 ]Department of Orthopedic Surgery, Rush University Medical Center, Chicago, Illinois, United States
                [2 ]Department of Orthopaedics, Massachusetts General Hospital, Yawkey Center for Outpatient Care, Boston, Massachusetts, United States
                [3 ]Department of Neurosurgery, Lin Shin Hospital, Taichung, Taiwan, Republic of China
                [4 ]Department of Orthopedics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan, Republic of China
                [5 ]Department of Orthopedics, First People's Hospital of Huaihua and University of South China, Huaihua, Hunan, People's Republic of China
                [6 ]Department of Orthopedic Surgery, Second Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China
                [7 ]Philadelphia Veterans Affairs Medical Center, Philadelphia, Pennsylvania, United States
                [8 ]Department of Physical Medicine and Rehabilitation, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States
                Author notes
                Address for correspondence Howard S. An, MD, Professor Department of Orthopedic Surgery, Rush University Medical Center 1653 W. Congress Parkway, Chicago, IL 60612United States howard.an@ 123456rushortho.com
                Article
                1500192
                10.1055/s-0036-1582391
                5110358
                27853661
                44937686-8b66-41b5-95bb-f3355eab9588
                © Thieme Medical Publishers
                History
                : 18 November 2015
                : 22 February 2016
                Categories
                Original Article

                cell therapy,human dermal fibroblast,disk degeneration,rabbit model

                Comments

                Comment on this article