Link N and Mesenchymal Stem Cells Can Induce Regeneration of the Early Degenerate Intervertebral Disc

Mwale, Fackson; Wang, Hong; Roughley, Peter J.; Antoniou, John; Haglund, Lisbet

doi:10.1089/ten.tea.2013.0749

Cited by 46 publications

(61 citation statements)

References 49 publications

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“…(2014) [80] could show successful MSC survival without any pre-conditioning with growth factors if injected into bovine coccygeal organ culture model along with the short peptide link-N. They injected only about 10 5 cells into the bovine disc and found a high cell viability after 21 days of organ culture.…”

Section: Organ Culture Biomaterials and Stem Cell Therapymentioning

confidence: 99%

“…During recent years the application of various hydrogels for NP and AF repair has been widely followed-up [80,82-85]. One approach is the injection of fibrin-genipin adhesive hydrogel to seal large AF defects [86,87].…”

Section: Organ Culture Biomaterials and Stem Cell Therapymentioning

confidence: 99%

“…The injection of short peptide sequences could be much more straightforward approach to be clinically feasible than the more risky methods involving autologous differentiated or progenitor cells. Here, Link N, a peptide sequence of Link protein, has been demonstrated to be a possible target for direct drug delivery [57,80]. Recent work by Mwale et al .…”

Section: Organ Culture Involving Human Ivdsmentioning

confidence: 99%

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Organ Culture Bioreactors – Platforms to Study Human Intervertebral Disc Degeneration and Regenerative Therapy

Gantenbein¹,

Illien-Jünger²,

Chan³

et al. 2015

CSCR

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In recent decades the application of bioreactors has revolutionized the concept of culturing tissues and organs that require mechanical loading. In intervertebral disc (IVD) research, collaborative efforts of biomedical engineering, biology and mechatronics have led to the innovation of new loading devices that can maintain viable IVD organ explants from large animals and human cadavers in precisely defined nutritional and mechanical environments over extended culture periods. Particularly in spine and IVD research, these organ culture models offer appealing alternatives, as large bipedal animal models with naturally occurring IVD degeneration and a genetic background similar to the human condition do not exist. Latest research has demonstrated important concepts including the potential of homing of mesenchymal stem cells to nutritionally or mechanically stressed IVDs, and the regenerative potential of “smart” biomaterials for nucleus pulposus or annulus fibrosus repair. In this review, we summarize the current knowledge about cell therapy, injection of cytokines and short peptides to rescue the degenerating IVD. We further stress that most bioreactor systems simplify the real in vivo conditions providing a useful proof of concept. Limitations are that certain aspects of the immune host response and pain assessments cannot be addressed with ex vivo systems. Coccygeal animal disc models are commonly used because of their availability and similarity to human IVDs. Although in vitro loading environments are not identical to the human in vivo situation, 3D ex vivo organ culture models of large animal coccygeal and human lumbar IVDs should be seen as valid alternatives for screening and feasibility testing to augment existing small animal, large animal, and human clinical trial experiments.

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Section: Organ Culture Biomaterials and Stem Cell Therapymentioning

confidence: 99%

Section: Organ Culture Biomaterials and Stem Cell Therapymentioning

confidence: 99%

Section: Organ Culture Involving Human Ivdsmentioning

confidence: 99%

See 1 more Smart Citation

Organ Culture Bioreactors – Platforms to Study Human Intervertebral Disc Degeneration and Regenerative Therapy

Gantenbein¹,

Illien-Jünger²,

Chan³

et al. 2015

CSCR

Self Cite

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“…Cryptic peptides [64] which recruit resident progenitor cells to sites of tissue damage to effect ECM/remodelling to promote repair processes have been described [65] and of relevance to repair of the degenerate IVD. Link-N, a cryptic fragment of linkprotein has been applied to a number of IVD studies and shown to stimulate the resident IVD cell populations as well as progenitor stem cells to upregulate production of collagen and aggrecan and stimulate repair of the degenerate IVD [66][67][68][69][70][71][72]. Future studies will hopefully uncover basic data applicable to the application of the resident progenitor stem cell population we have observed as a therapeutic cell type.…”

Section: Spine Research Issn 2471-8173mentioning

confidence: 99%

A Global Pictorial Assessment of the Intervertebral Disc Cell in Several Species Reveals a Remarkable Biodiversity in this Cell Type which should be taken into Account in Experimental Studies on Intervertebral Disc Repair

Melrose¹

2016

Spine Res

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“…Moreover, MSCs induce nucleous pulposus cells to suppress MMPs and inflammatory cytokine production in vitro (94). MSCs when administered together with Link-N can restore GAGs content and increase the expression of collagen type II in bovine mild degenerated discs (95). In clinical studies, injection of autologous bone marrow MSCs into nucleous pulposus improved pain and disability and water content was increased; albeit, disc height was not restored at 12-months postinjection (96).…”

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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Link N and Mesenchymal Stem Cells Can Induce Regeneration of the Early Degenerate Intervertebral Disc

Cited by 46 publications

References 49 publications

Organ Culture Bioreactors – Platforms to Study Human Intervertebral Disc Degeneration and Regenerative Therapy

Organ Culture Bioreactors – Platforms to Study Human Intervertebral Disc Degeneration and Regenerative Therapy

A Global Pictorial Assessment of the Intervertebral Disc Cell in Several Species Reveals a Remarkable Biodiversity in this Cell Type which should be taken into Account in Experimental Studies on Intervertebral Disc Repair

Biologic Treatment of Mild and Moderate Intervertebral Disc Degeneration

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