Biological Treatment Approaches for Degenerative Disk Disease: A Literature Review of In Vivo Animal and Clinical Data

Editorial Review

Biological Treatment Approaches for Degenerative Disk Disease: A Literature Review of In Vivo Animal and Clinical Data

Yu Moriguchi, Marjan Alimi, Thamina Khair, George Manolarakis, Connor Berlin, Lawrence J. Bonassar, Roger Härtl

Global Spine J 2016;6:497–518

JACO Editorial Reviewer: Gregory C. Priest, DC, FACO

Published: December 2017
Journal of the Academy of Chiropractic Orthopedists
December 2017, Volume 14, Issue 4

The original article copyright belongs to the original publisher. This review is available from: http://www.dcorthoacademy.com

© 2017 Priest and the Academy of Chiropractic Orthopedists. This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

AUTHORS’ ABSTRACT

Study Design: Literature review

Objective: Degenerative disk disease (DDD) has a negative impact on quality of life and is a major cause of morbidity worldwide. There has been a growing interest in the biological repair of DDD by both researchers and clinicians alike. To generate an overview of the recent progress in reparative strategies for the treatment of DDD highlighting their promises and limitations, a comprehensive review of the current literature was performed elucidating data from in vivo animal and clinical studies.

Methods: Articles and abstracts available in electronic databases of PubMed, Web of Science, and Google Scholar as of December 2014 were reviewed. Additionally, data from unpublished, ongoing clinical trials was retrieved from clinicaltrials.gov and available abstracts from research forums. Data was extracted from the most recent in vivo animal or clinical studies involving any of the following: (1) treatment with biomolecules, cells, or tissue-engineered constructs and (2) annulus fibrosus repair.

Results: Seventy-five articles met the inclusion criteria for review. Among these, 17 studies involved humans; 37, small quadrupeds; and 21, large quadrupeds. Findings from all treatments employed demonstrated improvement either in regenerative capacity or in pain attenuation, with the exception of one clinical study.

Conclusion: Published clinical studies on cell therapy have reported encouraging results in the treatment of DDD and resultant back pain. We expect new data to emerge in the near future as treatments for DDD continue to evolve in parallel to our greater understanding of disk health and pathology.

Keywords: Intervertebral disk, disk regeneration, back pain, growth factor, cell therapy, platelet-rich plasma, tissue engineering, annular repair

Clinical Relevance

The prevalence of degenerative disk disease is ubiquitous, reportedly occurring in more than 90% of people over 50 years of age. Degenerative disk disease can result in chronic back pain and frequently results in surgical intervention in an attempt to alleviate the related pain and disability. Unfortunately, the surgery itself may result in altered spinal biomechanics with secondary adjacent segment degeneration. Current treatment options do not adequately address the actual diseased tissue, the degenerated disk. This robustly-referenced literature review explores biologic treatment options that may hold promise for direct treatment of the degenerated disk.

JACO Editorial Summary:

  • The intervertebral disk (IVD) is a complex of three tissues: the nucleus pulposus (NP), the annulus fibrosus (AF), and the cartilaginous end plates.
  • Degenerative disk disease is a multifactorial process that involves one or more of the three tissues comprising the IVD complex.
  • Intervertebral disk degeneration is said to occur in 40% of persons younger than 30 years of age, and in more than 90% of those older than 50.
  • Degenerative disk disease (DDD) can lead to chronic lower back pain and disability.
  • Surgical intervention for DDD is reported to be performed in nearly 4 million patients worldwide.
  • Spinal fusion surgery presents risks for pseudarthrosis and adjacent segment degeneration, resulting in higher rates of reoperation.
  • This literature review evaluates in vivo animal and clinical data, with strong inclusion/exclusion criteria, and gives consideration to published data as well as data from ongoing, unpublished clinical studies.
  • Biological repair of the degenerated IVD are classified into three categories: biomolecular therapy, cell therapy, and tissue-engineered IVD construction. These treatment strategies are further stratified into categories specific to the stage of degeneration.
  • The goal of biologic treatment of the degenerated IVD is to repair/reconstruct the actual diseased tissue.
  • Biomolecular treatment may include protein injection, gene therapy and platelet-rich plasma.
  • Cell therapy may include differentiated cells such as disk-relevant cells and articular chondrocytes, and stem cells.
  • Tissue-engineering strategies may include scaffold development and whole disk transplantation with tissue-engineered construct.
  • The authors acknowledge the difficulties associated with extrapolation of data from animal studies to human applications, and are aware of model-based limitations such as subjective assessment of pain and physical function.
  • The authors feel that significant progress within the field of biologic therapies for DDD has been made in the past decade, although there are a paucity of clinical studies. They have attempted to consolidate and analyze a plethora of data from published and ongoing research.

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