Cell-Based Therapies for Lumbar Discogenic Low Back Pain

Wu, Tao; Song, Huaxin; Yan, Dong; Li, Jianhua

doi:10.1097/brs.0000000000001549

Cited by 33 publications

(18 citation statements)

References 35 publications

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“…Since cell viability is impaired in the degenerated IVD [ 16 ], NCM alone may not be sufficient. In this respect, intradiscal MSC transplantation is considered a promising regeneration strategy, currently explored in clinical trials (NCT01290367, NCT02412735) [ 17 ]. Therefore, the second aim of this study was to determine the effects of NCM combined with MSCs on degenerated canine IVDs in vivo .…”

Section: Introductionmentioning

confidence: 99%

Biologic canine and human intervertebral disc repair by notochordal cell-derived matrix: from bench towards bedside

et al. 2018

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The socioeconomic burden of chronic back pain related to intervertebral disc (IVD) disease is high and current treatments are only symptomatic. Minimally invasive strategies that promote biological IVD repair should address this unmet need. Notochordal cells (NCs) are replaced by chondrocyte-like cells (CLCs) during IVD maturation and degeneration. The regenerative potential of NC-secreted substances on CLCs and mesenchymal stromal cells (MSCs) has already been demonstrated. However, identification of these substances remains elusive. Innovatively, this study exploits the regenerative NC potential by using healthy porcine NC-derived matrix (NCM) and employs the dog as a clinically relevant translational model. NCM increased the glycosaminoglycan and DNA content of human and canine CLC aggregates and facilitated chondrogenic differentiation of canine MSCs in vitro. Based on these results, NCM, MSCs and NCM+MSCs were injected in mildly (spontaneously) and moderately (induced) degenerated canine IVDs in vivo and, after six months of treatment, were analyzed. NCM injected in moderately (induced) degenerated canine IVDs exerted beneficial effects at the macroscopic and MRI level, induced collagen type II-rich extracellular matrix production, improved the disc height, and ameliorated local inflammation. MSCs exerted no (additive) effects. In conclusion, NCM induced in vivo regenerative effects on degenerated canine IVDs. NCM may, comparable to demineralized bone matrix in bone regeneration, serve as ‘instructive matrix’, by locally releasing growth factors and facilitating tissue repair. Therefore, intradiscal NCM injection could be a promising regenerative treatment for IVD disease, circumventing the cumbersome identification of bioactive NC-secreted substances.

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Section: Introductionmentioning

confidence: 99%

Biologic canine and human intervertebral disc repair by notochordal cell-derived matrix: from bench towards bedside

et al. 2018

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“…At present, the clinical application of regenerative medicine strategies is limited to mesenchymal stem cell (MSC)/bone marrow aspirate, platelet‐rich plasma (PRP), and chondrocytes. The number of studies and the number of patients recruited are also limited . With regards to MSC therapy, feasibility and safety have been suggested in pilot clinical studies among chronic back pain patients .…”

Section: Available Clinical Treatments For Discogenic Painmentioning

confidence: 99%

“…The number of studies and the number of patients recruited are also limited. (121,122) With regards to MSC therapy, feasibility and safety have been suggested in pilot clinical studies among chronic back pain patients. (123)(124)(125) Analgesic effect, functional improvement, and increased water content by MSC injection therapy have also been reported, although there was no effect on recovering disc height.…”

Section: Regenerative Medicinementioning

confidence: 99%

Discogenic Back Pain: Literature Review of Definition, Diagnosis, and Treatment

et al. 2019

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Discogenic back pain is multifactorial; hence, physicians often struggle to identify the underlying source of the pain. As a result, discogenic back pain is often hard to treat—even more so when clinical treatment strategies are of questionable efficacy. Based on a broad literature review, our aim was to define discogenic back pain into a series of more specific and interacting pathologies, and to highlight the need to develop novel approaches and treatment strategies for this challenging and unmet clinical need. Discogenic pain involves degenerative changes of the intervertebral disc, including structural defects that result in biomechanical instability and inflammation. These degenerative changes in intervertebral discs closely intersect with the peripheral and central nervous systems to cause nerve sensitization and ingrowth; eventually central sensitization results in a chronic pain condition. Existing imaging modalities are nonspecific to pain symptoms, whereas discography methods that are more specific have known comorbidities based on intervertebral disc puncture and injection. As a result, alternative noninvasive and specific diagnostic methods are needed to better diagnose and identify specific conditions and sources of pain that can be more directly treated. Currently, there are many treatments/interventions for discogenic back pain. Nevertheless, many surgical approaches for discogenic pain have limited efficacy, thus accentuating the need for the development of novel treatments. Regenerative therapies, such as biologics, cell‐based therapy, intervertebral disc repair, and gene‐based therapy, offer the most promise and have many advantages over current therapies. © 2019 The Authors. JBMR Plus Published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research

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“…Inclusion criteria for recently reported clinical trials for regenerative cell-based therapies involved persistent lumbar discogenic low back pain for more than 6 months, and degenerative changes in the IVD (Pfirrmann grade 3 and more, disc height loss over 50%, positive provocative discography). 125 While chronic low back pain patients can have multiple sources of pain that do not directly come from IVD pathology, it is notable that clinical trials on cell therapy injections into IVDs appear to have potential to improve painful conditions. 126 Furthermore, IVD repair techniques have potential to repair or reverse degenerative changes in IVDs but would not address degenerative changes in facet joints or other spinal deformity conditions that would likely require augmentation with instrumentation.…”

Section: Clinical Translationmentioning

confidence: 99%

Critical aspects and challenges for intervertebral disc repair and regeneration—Harnessing advances in tissue engineering

et al. 2018

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Low back pain represents the highest burden of musculoskeletal diseases worldwide and intervertebral disc degeneration is frequently associated with this painful condition. Even though it remains challenging to clearly recognize generators of discogenic pain, tissue regeneration has been accepted as an effective treatment option with significant potential. Tissue engineering and regenerative medicine offer a plethora of exploratory pathways for functional repair or prevention of tissue breakdown. However, the intervertebral disc has extraordinary biological and mechanical demands that must be met to assure sustained success. This concise perspective review highlights the role of the disc microenvironment, mechanical and clinical design considerations, function vs mimicry in biomaterial‐based and cell engineering strategies, and potential constraints for clinical translation of regenerative therapies for the intervertebral disc.

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Cell-Based Therapies for Lumbar Discogenic Low Back Pain

Abstract: 4.

Cited by 33 publications

References 35 publications

Biologic canine and human intervertebral disc repair by notochordal cell-derived matrix: from bench towards bedside

Biologic canine and human intervertebral disc repair by notochordal cell-derived matrix: from bench towards bedside

Discogenic Back Pain: Literature Review of Definition, Diagnosis, and Treatment

Critical aspects and challenges for intervertebral disc repair and regeneration—Harnessing advances in tissue engineering

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