Innovative strategies for intervertebral disc regenerative medicine: From cell therapies to multiscale delivery systems

Henry, Nina; Clouet, Johann; Bideau, Jean Le; Visage, Catherine Le; Guicheux, Jérôme

doi:10.1016/j.biotechadv.2017.11.009

Cited by 99 publications

(81 citation statements)

References 150 publications

(167 reference statements)

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“…In reality, however, IVD does not possess the capacity for regeneration following degeneration. Some authors proposed that this may be attributed to the distinct and harsh biophysicochemical microenvironment of IVD [Henry et al, 2018].…”

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confidence: 99%

The Influence of Hyperosmolarity in the Intervertebral Disc on the Proliferation and Chondrogenic Differentiation of Nucleus Pulposus-Derived Mesenchymal Stem Cells

Wang

et al. 2018

Cells Tissues Organs

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Nucleus pulposus-derived mesenchymal stem cells (NP-MSCs) are suitable cell candidates for intervertebral disc (IVD) regeneration. However, little work has been done to determine the proliferation and chondrogenic differentiation of NP-MSCs in the hyperosmotic microenvironment of IVD. This study aimed to investigate the influence of the hyperosmolarity of IVD on the proliferation and chondrogenic differentiation of NP-MSCs. NP-MSCs were cultured in media of 300, 400, 430, and 500 mOsm/L, mimicking the osmotic pressures of serious degenerative, moderately degenerative, and healthy IVD. Cell proliferation was measured by CCK-8 assay. The expression of aggrecan, collagen I, and collagen II were measured by gene and protein expression analysis. Alcian blue and dimethylmethylene blue assay were used to investigate the accumulation of sulfate glycosaminoglycan. The regulation role of extracellular signal-regulated kinase (ERK) pathway was also analyzed. The results showed that, compared to 300 mOsm/L, hyperosmolarity of healthy IVD (430 and 500 mOsm/L) inhibited the proliferation and chondrogenic differentiation of NP-MSCs. The relative hypoosmotic condition of moderately degenerative IVD (400 mOsm/L) led to great proliferation and chondrogenic differentiation capacity. The ERK pathway was activated by the hyperosmolarity; inhibition of the ERK pathway abolished the difference in cell proliferation between the 300 mOsm/L and the hyperosmotic conditions, and enhanced chondrogenic differentiation. In conclusion, hyperosmolarity of IVD had a significant impact on the proliferation and chondrogenic differentiation of NP-MSCs. The ERK pathway was involved in the inhibition of proliferation and chondrogenic differentiation of NP-MSCs by the hyperosmolarity of IVD. The relative hypo-osmotic condition prevailing in degenerative discs offers a more permissive microenvironment for NP-MSCs.

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confidence: 99%

The Influence of Hyperosmolarity in the Intervertebral Disc on the Proliferation and Chondrogenic Differentiation of Nucleus Pulposus-Derived Mesenchymal Stem Cells

Wang

et al. 2018

Cells Tissues Organs

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“…Meanwhile, this kind of cell also characteristically expresses the surface protein molecules of mesenchymal stem cells, which can complete the three-line induced differentiation. Therefore, such cells are named as nucleus pulposus mesenchymal stem cells (NPMSCs) [10][11][12].…”

Section: Discussionmentioning

confidence: 99%

Effect of Lentivirus-mediated GDF5 Transfection on Differentiation of Rabbit Nucleus Pulposus Mesenchymal Stem Cells

Zhu

Zhao

et al. 2020

Preprint

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Abstract Background: Disc degenerative disease is a common senile degenerative disease, which seriously affects the quality of life of patients.The purpose of this study is to observe the biological and cytological characteristics of rabbit nucleus pulposus mesenchymal stem cells (NPMSCs), and to determine the effect of growth differentiation factor 5(GDF5) on the differentiation of rabbit NPMSCs by lentivirus transfection.Methods: In vitro culture model of rabbit NPMSCs was established and NPMSCs cells were identified by flow cytometry (FCM)and quantitative real-time PCR(qRT-PCR). Then NPMSCs were divided into three groups: lentiviral vector carrying GDF5 was used to transfect NPMSCs, to determine the transfection rate, which was recorded as transfection group, and the NPMSCs transfected with ordinary lentiviral vector was recorded as control group, NPMSCs without processing was recorded as normal group. FCM, qRT-PCR and Western Blot(WB) were used to detected the change of NPMSCs.Results: The transfected NPMSCs by GDF5 became longer and narrower, and the cell density decreased,and the positive rate of GDF5 in the transfected group was significantly higher than that in the other two groups (P<0.05). The mRNA expression of KRT8, KRT18, KRT19 in the transfected group was significantly higher than the other two groups(P<0.05),the result of WB were the same to qRT-PCR. Conclusions: GDF5 can induce the differentiation of NPMSCs and repair degenerative intervertebral discs. Lentiviral vector carrying GDF5 can be integrated into the chromosome genome of NPMSCs and promote differentiation of NPMSCs into nucleus pulposus cells(NPCs).

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“…To our knowledge, NP cells are one of the most component and functional cells, which play a critical role in producing proteoglycans (mainly aggrecan), hydrated extracellular matrix (ECM), and type II collagen in NP tissues, thereby supporting disc compression/decompression (Henry, Clouet, Le Bideau, Le Visage, & Guicheux, 2018). When IDD occurs, NP cells suffer from uptake proinflammatory cytokines, apoptosis stimulators, and increased levels of degrading enzymes (Hua et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Andrographolide prevents human nucleus pulposus cells against degeneration by inhibiting the NF‐κB pathway

Liu

Jiang

et al. 2018

Journal Cellular Physiology

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Intervertebral disc degeneration (IDD) is among the most common spinal disorders, pathologically characterized by excessive cell apoptosis and production of proinflammatory factors. Pharmacological targeting of nucleus pulposus (NP) degeneration may hold promise in IDD therapy, but it is limited by adverse side effects and nonspecificity of drugs. In this study, we used a natural compound, andrographolide (ANDRO), which has been widely used to intervene inflammatory and apoptotic diseases in the investigation of NP degeneration based on IDD‐patients‐derived NP cells by lipopolysaccharide (LPS) treatment for the preservation of degeneration. The results showed that LPS maintained the degeneration status of NP cells as evidenced by a high apoptosis rate and the expression of degenerative and inflammatory mediators after LPS treatment. ANDRO reversed the effects of LPS‐caused degeneration of NP cells and maintained the phenotype of NP cells, as demonstrated by flow cytometry, degenerative mediators (ADAMTS4 and ADAMTS5), inflammatory factors (COX2, PGE2, MMP‐13, and MMP‐3), biomarkers of NP cells (SOX9, ACAN, and COL2A1) expressions, and glycosaminoglycan secretion. We also found the involvement of the nuclear factor kappa‐light‐chain‐enhancer of the activated B cells (NF‐κB) pathway in ANDRO treatment, indicating that ANDRO prevented the LPS‐preserved degeneration of NP cells by inhibiting the NF‐κB pathway. This study may provide a reference for clinic medication of IDD therapy.

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Innovative strategies for intervertebral disc regenerative medicine: From cell therapies to multiscale delivery systems

Cited by 99 publications

References 150 publications

The Influence of Hyperosmolarity in the Intervertebral Disc on the Proliferation and Chondrogenic Differentiation of Nucleus Pulposus-Derived Mesenchymal Stem Cells

The Influence of Hyperosmolarity in the Intervertebral Disc on the Proliferation and Chondrogenic Differentiation of Nucleus Pulposus-Derived Mesenchymal Stem Cells

Effect of Lentivirus-mediated GDF5 Transfection on Differentiation of Rabbit Nucleus Pulposus Mesenchymal Stem Cells

Andrographolide prevents human nucleus pulposus cells against degeneration by inhibiting the NF‐κB pathway

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