Cell therapy for intervertebral disc repair: advancing cell therapy from bench to clinics

Abstract

Intervertebral disc (IVD) degeneration is a major cause of pain and disability; yet therapeutic options are limited and treatment often remains unsatisfactory. In recent years, research activities have intensified in tissue engineering and regenerative medicine, and pre-clinical studies have demonstrated encourageing results. Nonetheless, the translation of new biological therapies into clinical practice faces substantial barriers. During the symposium “Where Science meets Clinics”, sponsored by the AO Foundation and held in Davos, Switzerland, from September 5–7, 2013, hurdles for translation were outlined, and ways to overcome them were discussed. With respect to cell therapy for IVD repair, it is obvious that regenerative treatment is indicated at early stages of disc degeneration, before structural changes have occurred. It is envisaged that in the near future, screening techniques and non-invasive imageing methods will be available to detect early degenerative changes. The promises of cell therapy include a sustained effect on matrix synthesis, inflammation control, and prevention of angio- and neurogenesis. Discogenic pain, originating from “black discs” or annular injury, prevention of adjacent segment disease, and prevention of post-discectomy syndrome were identified as prospective indications for cell therapy. Before such therapy can safely and effectively be introduced into clinics, the identification of the patient population and proper standardisation of diagnostic parameters and outcome measurements are indispensable. Furthermore, open questions regarding the optimal cell type and delivery method need to be resolved in outline order to overcome the safety concerns implied with certain procedures. Finally, appropriate large animal models and well-designed clinical studies will be required, particularly addressing safety aspects.

Cell-Based Therapies for Lumbar Discogenic Low Back Pain

“…In pre-clinical research, one of three biological approaches is typically used to address the degenerative process: stimulating anabolic processes; modulating catabolic processes; and providing new cells 22 . Tissue-engineered cellular therapy has focused on chondrocyte 23 or stem cell replacement therapy 24 .…”

Biomaterials for intervertebral disc regeneration and repair

“…During the degenerative process, the end plates thin and mineralize (58) and permeability of the end plates may decrease and hinder nutrient transport to the IVD. Strategies that serve to increase permeability of the endplates, and thus maintain nutrition to the IVD may be helpful to support the long-term survival of the endogenous or delivered cell populations (28–30, 59, 60). An increased presence of nociceptive nerve fibers in the end plates of pathological motion segments is believed to be related to painful conditions with IVD disorders (61) but is very poorly understood.…”

“…There are a very large number of pre-clinical and now clinical studies that reported on outcomes for injection of allogeneic and autologous progenitor and stem cell populations to the IVD (see discussions in (27), (28)), and we provide a brief overview of those clinical studies that make use of biomaterials for cell or drug delivery. The outcomes for cell or drug delivery may have some overlap with the goals of engineered material approaches to restore IVD anatomy (e.g., disc height) to prevent neural impingements and associated pain, or to reverse the radiographic evidence of pathology (e.g., signal intensity upon MRI); however, the challenges to regulatory approval and high demand for cell delivery to the IVD have driven work past a mechanistic or consensus-based understanding of best practice.…”

Biological challenges for regeneration of the degenerated disc using cellular therapies

“…2014, Benneker et al. 2014, Sakai and Andersson 2015). Patients come to see a clinician because they have back pain, not because they are worried about disc degeneration.…”