Intervertebral disc regeneration or repair with biomaterials and stem cell therapy - feasible or fiction?

Chan, Samantha; Gantenbein, Benjamin

doi:10.4414/smw.2012.13598

Cited by 56 publications

(64 citation statements)

References 97 publications

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“…Various organ culture systems have been in development and use: (1) culture of discs without endplates (Chiba et al, 1998), (2) with vertebral bone (Lee et al, 2006;IllienJunger et al, 2010;Chan and Gantenbein-Ritter, 2012b) and (3) with cartilaginous endplates Jim et al, 2011). Organ culture systems except for those retaining only the cartilaginous endplate model were unable to maintain high cell viability even for short durations of culture; whereas the cartilaginous endplate model for human disc culture developed by us has overcome this problem.…”

Section: Discussionmentioning

confidence: 99%

“…Many strategies have been proposed and a few tested to repair and/or regenerate IVDs biologically. Among them the most common ones evaluated are injection of growth factors or bioactive peptides, gene therapy, cell injections, and implantation of hydrogel-based medical devices (Chadderdon et al, 2004;Anderson et al, 2005;Boyd and Carter, 2006;Zhao et al, 2007;Woods et al, 2011;Chan and Gantenbein-Ritter, 2012a).…”

Section: Introductionmentioning

confidence: 99%

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Best Paper NASS 2013: Link-N can stimulate proteoglycan synthesis in the degenerated human intervertebral discs

Gawri¹,

Antoniou²,

Ouellet³

et al. 2013

eCM

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Intervertebral disc (IVD) degeneration is the most common cause of back pain. Presently there is no medical treatment, leaving surgery as the only offered option. Here we evaluate the potential of Link-N to promote extracellular matrix regeneration in human IVDs. Human disc cells cultured in alginate and intact human discs were exposed to a combination of Link-N and 35 SO 4 in the presence or absence of interleukin (IL)-1, and the effect on proteoglycan synthesis was evaluated. In addition, message levels of aggrecan, matrix metalloproteinase (MMP)-3, MMP-13, a Disintegrin And Metalloproteinase with Thrombospondin Motifs (ADAMTS)-4 and ADAMTS-5 were evaluated in alginate cultures. Human disc cells responded in a dose dependent manner with maximal proteoglycan synthesis at 1 µg/mL Link-N. Link-N treatment also induced proteoglycan synthesis in intact human discs, and a prolonged effect was found up to one week after Link-N treatment. Message levels of proteinases were decreased by Link-N in the presence of IL-1. Thus, Link-N can promote proteoglycan synthesis and deplete proteinase expression in adult human discs. Link-N could therefore be a promising candidate for biologically-induced disc repair, and could provide an alternative to surgical intervention for early stage disc degeneration.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Best Paper NASS 2013: Link-N can stimulate proteoglycan synthesis in the degenerated human intervertebral discs

Gawri¹,

Antoniou²,

Ouellet³

et al. 2013

eCM

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“…A limitation of the above methods is that differentiation of MSCs might be in- conclusive, and, furthermore, it is unclear whether differentiated cells remain intact or capable for replication. Autologous bone marrow-derived MSCs are proliferating, differentiating into nucleous pulposus cell phenotype, and preserve water content and disc height into canine, porcine and rabbit models (92). Transplantation of MSCs in a rabbit degenerated intervertebral disc resulted in deceleration of disc height loss and increase in T2-weighted signal intensity.…”

Section: Cell Replacementmentioning

confidence: 99%

Biologic Treatment of Mild and Moderate Intervertebral Disc Degeneration

Vasiliadis

Pneumaticos

Evangelopoulos

et al. 2014

Mol Med

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Disc degeneration is the most common cause of back pain in adults and has enormous socioeconomic implications. Conservative management is ineffective in most cases, and results of surgical treatment have not yet reached desirable standards. Biologic treatment options are an alternative to the above conventional management and have become very attractive in recent years. The present review highlights the currently available biologic treatment options in mild and moderate disc degeneration, where a potential for regeneration still exists. Biologic treatment options include protein-based and cell-based therapies. Proteinbased therapies involve administration of biologic factors into the intervertebral disc to enhance matrix synthesis, delay degeneration or impede inflammation. These factors can be delivered by an intradiscal injection, alone or in combination with cells or tissue scaffolds and by gene therapy. Cell-based therapies comprise treatment strategies that aim to either replace necrotic or apoptotic cells, or minimize cell death. Cell-based therapies are more appropriate in moderate stages of degenerated disc disease, when cell population is diminished; therefore, the effect of administration of growth factors would be insufficient. Although clinical application of biologic treatments is far from being an everyday practice, the existing studies demonstrate promising results that will allow the future design of more sophisticated methods of biologic intervention to treat intervertebral disc degeneration.

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“…1). Cells, in particular mesenchymal stromal cells (MSCs), and growth factors hold promise to directly regenerate IVD tissue by anabolic effects on the cell population and matrix homeostasis (Chan and Gantenbein-Ritter, 2012;Masuda, 2008;Richardson and Hoyland, 2008;Yim et al, 2014). In contrast, biomaterials can have several roles.…”

Section: Regenerative Medicine (Rm) As Emerging Approach For Ivd Degementioning

confidence: 99%

Biomaterials for intervertebral disc regeneration: past performance and possible future strategies

Schutgens¹,

Tryfonidou²,

Smit³

et al. 2015

eCM

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Intervertebral disc (IVD) degeneration is associated with most cases of cervical and lumbar spine pathologies, amongst which chronic low back pain has become the number one cause of loss of quality-adjusted life years. In search of alternatives to the current less than optimal and usually highly invasive treatments, regenerative strategies are being devised, none of which has reached clinical practice as yet. Strategies include the use of stem cells, gene therapy, growth factors and biomaterial carriers. Biomaterial carriers are an important component in musculoskeletal regenerative medicine techniques. Several biomaterials, both from natural and synthetic origin, have been used for regeneration of the IVD in vitro and in vivo. Aspects such as ease of use, mechanical properties, regenerative capacity, and their applicability as carriers for regenerative and anti-degenerative factors determine their suitability for IVD regeneration. The current review provides an overview of the biomaterials used with respect to these properties, including their drawbacks. In addition, as biomaterial application until now appears to have been based on a mix of mere availability and intuition, a more rational design is proposed for future use of biomaterials for IVD regeneration. Ideally, high-throughput screening is used to identify optimally effective materials, or alternatively medium content comparative studies should be carried out to determine an appropriate reference material for future studies on novel materials.

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Intervertebral disc regeneration or repair with biomaterials and stem cell therapy - feasible or fiction?

Cited by 56 publications

References 97 publications

Best Paper NASS 2013: Link-N can stimulate proteoglycan synthesis in the degenerated human intervertebral discs

Best Paper NASS 2013: Link-N can stimulate proteoglycan synthesis in the degenerated human intervertebral discs

Biologic Treatment of Mild and Moderate Intervertebral Disc Degeneration

Biomaterials for intervertebral disc regeneration: past performance and possible future strategies

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