Novel therapeutic strategies for degenerative disc disease: Review of cell biology and intervertebral disc cell therapy

Fernandez-Moure, Joseph; Moore, Carol L.; Kim, Keemberly; Karim, Azim; Smith, Kevin M.; Barbosa, Zonia; Eps, Jeffrey L. Van; Rameshwar, Pranela; Weiner, Bradley K.

doi:10.1177/2050312118761674

Cited by 53 publications

(44 citation statements)

References 94 publications

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“…The most appealing solution to regenerate the NP at the present time seems to be the design of proper scaffolds that could provide transplanted MSCs with an adequate three-dimensional microenvironment. The ideal scaffold should be biocompatible and easy to manipulate, while biomechanically stable and respectful to cell morphology and functionality [133]. To date, various biomaterials including HA, collagen, fibrin, alginate, gelatin, and silk have been investigated as scaffolds for cell engraftment and IVD regeneration [12].…”

Section: Under Inflammatory Conditions Adscs Have Beenmentioning

confidence: 99%

Interaction between Mesenchymal Stem Cells and Intervertebral Disc Microenvironment: From Cell Therapy to Tissue Engineering

Vadalà

Ambrosio

Russo

et al. 2019

Stem Cells International

112

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Low back pain (LBP) in one of the most disabling symptoms affecting nearly 80% of the population worldwide. Its primary cause seems to be intervertebral disc degeneration (IDD): a chronic and progressive process characterized by loss of viable cells and extracellular matrix (ECM) breakdown within the intervertebral disc (IVD) especially in its inner region, the nucleus pulposus (NP). Over the last decades, innovative biological treatments have been investigated in order to restore the original healthy IVD environment and achieve disc regeneration. Mesenchymal stem cells (MSCs) have been widely exploited in regenerative medicine for their capacity to be easily harvested and be able to differentiate along the osteogenic, chondrogenic, and adipogenic lineages and to secrete a wide range of trophic factors that promote tissue homeostasis along with immunomodulation and anti-inflammation. Several in vitro and preclinical studies have demonstrated that MSCs are able to acquire a NP cell-like phenotype and to synthesize structural components of the ECM as well as trophic and anti-inflammatory mediators that may support resident cell activity. However, due to its unique anatomical location and function, the IVD presents distinctive features: avascularity, hypoxia, low glucose concentration, low pH, hyperosmolarity, and mechanical loading. Such conditions establish a hostile microenvironment for both resident and exogenously administered cells, which limited the efficacy of intradiscal cell therapy in diverse investigations. This review is aimed at describing the characteristics of the healthy and degenerated IVD microenvironment and how such features influence both resident cells and MSC viability and biological activity. Furthermore, we focused on how recent research has tried to overcome the obstacles coming from the IVD microenvironment by developing innovative cell therapies and functionalized bioscaffolds.

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Section: Under Inflammatory Conditions Adscs Have Beenmentioning

confidence: 99%

Interaction between Mesenchymal Stem Cells and Intervertebral Disc Microenvironment: From Cell Therapy to Tissue Engineering

Vadalà

Ambrosio

Russo

et al. 2019

Stem Cells International

112

View full text Add to dashboard Cite

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“…Intervertebral disc (IVD) degeneration is one of the major causes of LBP 12,13 . An important composition to maintain the IVD biomechanical performance is the nucleus pulposus (NP), which undergoes cellular and extracellular matrix (ECM) changes during IVD degeneration at the early pathological stage 4 .…”

Section: Introductionmentioning

confidence: 99%

Mechanisms of endogenous repair failure during intervertebral disc degeneration

Ma¹,

Chen²,

et al. 2019

Osteoarthritis and Cartilage

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Intervertebral disc (IVD) degeneration is frequently associated with Low back pain (LBP), which can severely reduce the quality of human life and cause enormous economic loss. However, there is a lack of long-lasting and effective therapies for IVD degeneration at present. Recently, stem cell based tissue engineering techniques have provided novel and promising treatment for the repair of degenerative IVDs. Numerous studies showed that stem/progenitor cells exist naturally in IVDs and could migrate from their niche to the IVD to maintain the quantity of nucleus pulposus (NP) cells. Unfortunately, these endogenous repair processes cannot prevent IVD degeneration as effectively as expected. Therefore, theoretical basis for regeneration of the NP in situ can be obtained from studying the mechanisms of endogenous repair failure during IVD degeneration. Although there have been few researches to study the mechanism of cell death and migration of stem/progenitor cells in IVD so far, studies demonstrated that the major inducing factors (compression and hypoxia) of IVD degeneration could decrease the number of NP cells by regulating apoptosis, autophagy, and necroptosis, and the particular chemokines and their receptors played a vital role in the migration of mesenchymal stem cells (MSCs). These studies provide a clue for revealing the mechanisms of endogenous repair failure during IVD degeneration. This article reviewed the current research situation and progress of the mechanisms through which IVD stem/progenitor cells failed to repair IVD tissues during IVD degeneration. Such studies provide an innovative research direction for endogenous repair and a new potential treatment strategy for IVD degeneration.

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“…DDD is defined as symptomatic intervertebral disc (IVD) degeneration, whereby nociception is thought to be linked to increased levels of proinflammatory cytokines within the tissue, including IL-1β, TNF-α, IL-6, IL-8, and IFN-γ (Wuertz and Haglund, 2013;Johnson et al, 2015). While current treatment options for DDD, including oral analgesics and surgery, solely aim to reduce the symptoms, researchers have made extensive efforts over the past decade to develop novel therapeutic approaches that target the underlying pathophysiological mechanisms, i.e., degeneration, inflammation, and enhanced apoptosis (Fernandez-Moure et al, 2018;Tendulkar et al, 2019). A wide range of approaches has been tested which are described in detail elsewhere (Krupkova et al, 2018;Smith et al, 2018;Clouet et al, 2019;Hodgkinson et al, 2019;Loibl et al, 2019), ranging from autologous disc cell therapy, growth factors, biologics, gene transfection, and biomaterials to CRISPR/Cas9 genome engineering, as well as the use of mesenchymal stem cells (MSCs).…”

Section: Introductionmentioning

confidence: 99%

Therapeutic Potential of Extracellular Vesicles in Degenerative Diseases of the Intervertebral Disc

Piazza

Dehghani

Gaborski

et al. 2020

Front. Bioeng. Biotechnol.

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Extracellular vesicles (EVs) are lipid membrane particles carrying proteins, lipids, DNA, and various types of RNA that are involved in intercellular communication. EVs derived from mesenchymal stem cells (MSCs) have been investigated extensively in many different fields due to their crucial role as regeneration drivers, but research for their use in degenerative diseases of the intervertebral disc (IVD) has only started recently. MSC-derived EVs not only promote extracellular matrix synthesis and proliferation in IVD cells, but also reduce apoptosis and inflammation, hence having multifunctional beneficial effects that seem to be mediated by specific miRNAs (such as miR-233 and miR-21) within the EVs. Aside from MSC-derived EVs, IVD-derived EVs (e.g., stemming from notochordal cells) also have important functions in IVD health and disease. This article will summarize the current knowledge on MSC-derived and IVDderived EVs and will highlight areas of future research, including the isolation and analysis of EV subpopulations or exposure of MSCs to cues that may enhance the therapeutic potential of released EVs.

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Novel therapeutic strategies for degenerative disc disease: Review of cell biology and intervertebral disc cell therapy

Cited by 53 publications

References 94 publications

Interaction between Mesenchymal Stem Cells and Intervertebral Disc Microenvironment: From Cell Therapy to Tissue Engineering

Interaction between Mesenchymal Stem Cells and Intervertebral Disc Microenvironment: From Cell Therapy to Tissue Engineering

Mechanisms of endogenous repair failure during intervertebral disc degeneration

Therapeutic Potential of Extracellular Vesicles in Degenerative Diseases of the Intervertebral Disc

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