Formation, function, and exhaustion of notochordal cytoplasmic vacuoles within intervertebral disc: current understanding and speculation

Wang, Feng; Gao, Zengxin; Cai, Feng; Sinkemani, Arjun; Xie, Zhi‐Yang; Shi, Rui; Wei, Ji-Nan

doi:10.18632/oncotarget.18101

Cited by 28 publications

(29 citation statements)

References 98 publications

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“…When the bony vertebra is formed, hyaline cartilage adjacent to the IVD is maintained and develops to the CEP at the end plate ( Figure 1). In the early stage of human life, the NP is populated by clusters of large, vacuolated notochordal cells and by small chondrocyte-like cells [13]. However, by the second decade of life, the notochordal cells in the NP disappear, and the NP transitions from a notochordal structure to a tissue embedded with small chondrocyte-like cells [14].…”

Section: The Development Of the Ivdmentioning

confidence: 99%

The Immune Privilege of the Intervertebral Disc: Implications for Intervertebral Disc Degeneration Treatment

Sun¹,

Liu²,

Luo³

2020

Int. J. Med. Sci.

131

138

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The intervertebral disc (IVD) is the largest avascular organ of the body. It is composed of three parts: the nucleus pulposus (NP), the annulus fibrosus (AF) and the cartilaginous endplate (CEP). The central NP is surrounded by the AF and sandwiched by the two CEPs ever since its formation. This unique structure isolates the NP from the immune system of the host. Additionally, molecular factors expressed in IVD have been shown inhibitive effect on immune cells and cytokines infiltration. Therefore, the IVD has been identified as an immune privilege organ. The steady state of immune privilege is fundamental to the homeostasis of the IVD. The AF and the CEP, along with the immunosuppressive molecular factors are defined as the blood-NP barrier (BNB), which establishes a strong barrier to isolate the NP from the host immune system. When the BNB is damaged, the auto-immune response of the NP occurs with various downstream cascade reactions. This effect plays an important role in the whole process of IVD degeneration and related complications, such as herniation, sciatica and spontaneous herniated NP regression. Taken together, an enhanced understanding of the immune privilege of the IVD could provide new targets for the treatment of symptomatic IVD disease. However, the underlying mechanism above is still not fully clarified. Accordingly, the current study will extensively review and discuss studies regarding the immune privilege of the IVD.

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Section: The Development Of the Ivdmentioning

confidence: 99%

The Immune Privilege of the Intervertebral Disc: Implications for Intervertebral Disc Degeneration Treatment

Sun¹,

Liu²,

Luo³

2020

Int. J. Med. Sci.

131

138

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“…Some scholars have found that human notochord cells gradually reduce with the growth of age and disc degeneration, this notochord cells are NPMSCs [17]. Rodrigues-pinto R et al found that keratin 8, 18, 19 (KRT8, KRT18, KRT19) are speci c markers of human notochord cells, and are expressed in all stages of notochord cells [18].…”

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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“…It is well known that species‐specific responses can be observed and as such, caution must be applied when using nonhuman cells in initial proof of principle testing. These differences could arise from differential species‐dependent expression of proteins and receptors, cell types isolated from tissues (eg, notochordal cells), or the disease status of the tissues . In view of the challenges in accessing human cells, the majority of animal cells utilized in initial experimental studies are from normal young adult animals, which do not represent the cellular phenotype seen within the degenerated (human) IVD, which are senescent and exhibit a catabolic phenotype which has implications on regenerative therapies .…”

Section: Bench Side Testing: In Vitro and Ex Vivo Testingmentioning

confidence: 99%

“…These differences could arise from differential species-dependent expression of proteins and receptors, cell types isolated from tissues (eg, notochordal cells), or the disease status of the tissues. [9][10][11] In view of the challenges in accessing human cells, the majority of animal cells utilized in initial experimental studies are from normal young adult animals, which do not represent the cellular phenotype seen within the degenerated (human) IVD, which are senescent and exhibit a catabolic phenotype which has implications on regenerative therapies. [12][13][14] Over the last 10 years, there has been increased research on human cell sources with approximately 50% of studies culturing IVD cells or cells for regeneration of the IVD sourced from human (Figure 2A,C).…”

Section: Species and Cell/tissue Sourcementioning

confidence: 99%

Leaping the hurdles in developing regenerative treatments for the intervertebral disc from preclinical to clinical

et al. 2018

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Chronic back and neck pain is a prevalent disability, often caused by degeneration of the intervertebral disc. Because current treatments for this condition are less than satisfactory, a great deal of effort is being applied to develop new solutions, including regenerative strategies. However, the path from initial promising idea to clinical use is fraught with many hurdles to overcome. Many of the keys to success are not necessarily linked to science or innovation. Successful translation to clinic will also rely on planning and awareness of the hurdles. It will be essential to plan your entire path to clinic from the outset and to do this with a multidisciplinary team. Take advice early on regulatory aspects and focus on generating the proof required to satisfy regulatory approval. Scientific demonstration and societal benefits are important, but translation cannot occur without involving commercial parties, which are instrumental to support expensive clinical trials. This will only be possible when intellectual property can be protected sufficiently to support a business model. In this manner, commercial, societal, medical, and scientific partners can work together to ultimately improve patient health. Based on literature surveys and experiences of the co‐authors, this opinion paper presents this pathway, highlights the most prominent issues and hopefully will aid in your own translational endeavors.

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Formation, function, and exhaustion of notochordal cytoplasmic vacuoles within intervertebral disc: current understanding and speculation

Cited by 28 publications

References 98 publications

The Immune Privilege of the Intervertebral Disc: Implications for Intervertebral Disc Degeneration Treatment

The Immune Privilege of the Intervertebral Disc: Implications for Intervertebral Disc Degeneration Treatment

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

Leaping the hurdles in developing regenerative treatments for the intervertebral disc from preclinical to clinical

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