Homing of Mesenchymal Stem Cells in Induced Degenerative Intervertebral Discs in a Whole Organ Culture System

Illien-Jünger, Svenja; Pattappa, Girish; Peroglio, Marianna; Benneker, Lorin Michael; Stoddart, Martin J.; Sakai, Daisuke; Mochida, Joji; Grad, Sibylle; Alini, Mauro

doi:10.1097/brs.0b013e3182544a8a

Cited by 87 publications

(86 citation statements)

References 48 publications

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“…Furthermore, MMPs and their inhibitors have also been shown to enhance MSC migratory capacity [213]. In a recent study, MSCs were recruited in vitro by conditioned medium from IVDs cultured under degenerative-simulated conditions [214]. CCL5/RANTES has been identified as a key chemoattractant released by degenerative IVD in organ culture [215].…”

Section: Cell-based Therapiesmentioning

confidence: 99%

Inflammation in intervertebral disc degeneration and regeneration

Molinos

Almeida

Caldeira

et al. 2015

J. R. Soc. Interface.

317

256

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Intervertebral disc (IVD) degeneration is one of the major causes of low back pain, a problem with a heavy economic burden, which has been increasing in prevalence as populations age. Deeper knowledge of the complex spatial and temporal orchestration of cellular interactions and extracellular matrix remodelling is critical to improve current IVD therapies, which have so far proved unsatisfactory. Inflammation has been correlated with degenerative disc disease but its role in discogenic pain and hernia regression remains controversial. The inflammatory response may be involved in the onset of disease, but it is also crucial in maintaining tissue homeostasis. Furthermore, if properly balanced it may contribute to tissue repair/regeneration as has already been demonstrated in other tissues. In this review, we focus on how inflammation has been associated with IVD degeneration by describing observational and in vitro studies as well as in vivo animal models. Finally, we provide an overview of IVD regenerative therapies that target key inflammatory players.

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Section: Cell-based Therapiesmentioning

confidence: 99%

Inflammation in intervertebral disc degeneration and regeneration

Molinos

Almeida

Caldeira

et al. 2015

J. R. Soc. Interface.

317

256

View full text Add to dashboard Cite

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“…We have demonstrated in an ex vivo model that human bone marrow derived MSCs were able to migrate through the endplate of an IVD maintained in organ culture [121]. Recruitment was significantly enhanced in IVDs cultured under induced degenerative conditions, including limited nutrition, high frequency loading and/or needle puncture [122].…”

Section: Progenitor Cell Homingmentioning

confidence: 98%

Advancing the cellular and molecular therapy for intervertebral disc disease

Sakai

Grad

2015

Advanced Drug Delivery Reviews

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246

220

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“…The model described in the present study has been validated in previous work (Illien-Junger et al, 2010;Illien-Junger et al, 2012). However, certain limitations need to be taken into consideration when comparing it to the situation in human disc degeneration.…”

Section: G Pattappa Et Al Ccl5/rantes Is Released By Intervertebral mentioning

confidence: 99%

CCL5/RANTES is a key chemoattractant released by degenerative intervertebral discs in organ culture

Pattappa

Peroglio²,

Sakai³

et al. 2014

eCM

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Release of chemotactic factors in response to tissue damage has been described for different musculoskeletal tissues, including the intervertebral disc (IVD). This study investigated the chemoattractants that are released by induced degenerative IVDs and may be involved in recruiting mesenchymal stem cells (MSCs). Bovine caudal discs were cultured within a bioreactor and loaded under conditions that mimicked physiological or degenerative settings. Between days 4-6, medium was replaced by PBS, which was subsequently used for proteomic, ELISA and immunoprecipitation analyses of secreted chemokines and cytokines. A Boyden chamber assay was used to observe human MSC migration towards native and chemokine depleted media. Gene expression levels of chemokine receptors in human MSCs were analysed, and CCL5 was localised in bovine and human IVD by immunohistochemistry. Proteomic analysis revealed the presence of CCL5 and CXCL6 within conditioned media. Higher concentrations of CCL5 were found in the degenerative media, and a relationship was found between interleukin-1β and CCL5 concentration. Chemokine immunoprecipitation showed that MSCs had a significantly reduced chemotactic migration towards CCL5-immunoprecipitated and CCL5/CXCL6 coimmunoprecipitated media, whilst CXCL6 depletion did not change MSC chemotaxis. MSCs showed a significant increase in mRNA expression of the CCL5 receptors, CCR1 and CCR4, upon culture in degenerative media. Furthermore, CCL5 was identified in bovine and human disc tissue by immunohistochemistry. Hence, CCL5 may be a key chemoattractant that is produced and released by the intervertebral disc cells. Therefore, these factors could be used to enhance stem/progenitor cell mobilisation in regenerative therapies for early stages of disc degeneration.

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Homing of Mesenchymal Stem Cells in Induced Degenerative Intervertebral Discs in a Whole Organ Culture System

Cited by 87 publications

References 48 publications

Inflammation in intervertebral disc degeneration and regeneration

Inflammation in intervertebral disc degeneration and regeneration

Advancing the cellular and molecular therapy for intervertebral disc disease

CCL5/RANTES is a key chemoattractant released by degenerative intervertebral discs in organ culture

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