Biological Behavior of Human Nucleus Pulposus Mesenchymal Stem Cells in Response to Changes in the Acidic Environment During Intervertebral Disc Degeneration

Liu, Jianjun; Tao, Hui; Wang, Hanbang; Dong, Fulong; Zhang, Renjie; Li, Jie; Ge, Peng; Song, Peiwen; Zhang, Huaqing; Xu, Peng; Li, Xiaoying; Shen, Cailiang

doi:10.1089/scd.2016.0314

Cited by 68 publications

(71 citation statements)

References 43 publications

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“…The survivability and function of the MSC are influenced by the microenvironment of the degenerative IVD niche . Tolerating hypertonic and acidic environment, endogenous MSC derived from NP has become promising candidate to repair and regenerate degenerative IVD . However, previous studies have revealed negative influences of a diabetic environment on NP and MSC, including decreased proliferation ability and increased cell apoptosis .…”

Section: Discussionmentioning

confidence: 99%

The effect of high glucose on the biological characteristics of nucleus pulposus‐derived mesenchymal stem cells

Liu

et al. 2020

Cell Biochemistry & Function

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Diabetes mellitus (DM) is a dependent risk factor in the progression of intervertebral disc degeneration (IVDD). High glucose supply has negative effects on nucleus pulpous (NP) cell and mesenchymal stem cell (MSC) biology. However, the effect of hyperglycaemia on the biological characterization of nucleus pulpous-derived mesenchymal stem cell (NPMSC) has not been investigated previously. Therefore, further exploration of the effects of DM-associated hyperglycaemia on NPMSC biology is important to better understand and develop endogenous repair strategies of DM patient-associated IVDD. Therefore, the cell biological characteristics were compared between NPMSC cultured in media with low glucose concentration (LG-NPMSC) and high glucose concentration (HG-NPMSC). The results demonstrated that HG-NPMSC showed significantly decreased cell proliferation, colony formation ability, migration and wound-healing capability compared with those of LG-NPMSC. HG-NPMSC also showed significantly decreased expressions of stemness genes and mRNA and protein expressions of silent information regulator protein 1 (SIRT1), SIRT6, hypoxia inducible factor-1α (HIF-1α) and glucose transporter 1 (GLUT-1), whereas increased cell apoptosis, cell senescence and caspase-3 expression. These results suggest that high glucose may decrease proliferation and stemness maintenance ability and increase apoptosis and senescence of NPMSC.Significance of the study: We found that high glucose concentration significantly decreased cell proliferation, colony formation ability, migration and wound-healing capability of nucleus pulposus-derived mesenchymal stem cells. Moreover, high glucose cultured nucleus pulposus-derived mesenchymal stem cells showed significantly decreased expression of stemness genes, related mRNA and protein, whereas increased cell apoptosis, cell senescence and expression of caspase-3. The present study indicated that better control of high concentration glucose in the early stage of diabetes mellitus should be recommended to prevent or limit intervertebral disc degeneration. K E Y W O R D S-high glucose, nucleus pulposus-derived mesenchymal stem cells, proliferation, apoptosis, senescence

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Section: Discussionmentioning

confidence: 99%

The effect of high glucose on the biological characteristics of nucleus pulposus‐derived mesenchymal stem cells

Liu

et al. 2020

Cell Biochemistry & Function

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“…It was generally accepted that MSCs repaired the damaged tissues mainly by differentiating into specific IVD cell types and replacing the lost IVD cells. But some studies demonstrated that stem cells secreted cytokines and growth factors that could influence NP cells, such as TGF-b and IGF-1 to inhibit NP cell senescence 93 , IGF-1 and bone morphogenetic protein (BMP)-7 to prevent NP cell apoptosis 50 , and TGF-b and BMP-7 to reduce decomposition of the cell matrix and inhibit inflammation in IVDs 85,94 . And it was reported that adipose-derived MSCs inhibited the apoptosis of NP cells by down-regulating the expression of caspase-3 and -9 in NP cells, and promoted NP cells to produce more ECM and suppressed the expression of matrix metalloproteinases, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTSs) as well as pro-inflammatory factors, which could induce NP cells to express tissue inhibitors of metalloproteinases (TIMPs), cytokeratin 8, and other cytokines 40,81,95 .…”

Section: Interactions Between Exogenous Mscs and Np Cellsmentioning

confidence: 99%

Mechanisms of endogenous repair failure during intervertebral disc degeneration

Ma¹,

Chen²,

et al. 2019

Osteoarthritis and Cartilage

103

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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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“…PCR results showed that hNP-MSCs cultured in hypoxia and nutrition deficiency had decreased expression of aggrecan, collagen type II and I, indicating that hypoxia and nutrition deficiency could lead to metabolic disturbance in hNP-MSCs. hNP-MSCs expressed stem cell-related genes (Oct4, Nanog, Jagged, and Notch1) [30] and hypoxia and nutrition deficiency downregulated the expression levels of these genes. Previous study found that hypoxia inhibited the viability and Fig.…”

Section: Discussionmentioning

confidence: 99%

The protective effects of PI3K/Akt pathway on human nucleus pulposus mesenchymal stem cells against hypoxia and nutrition deficiency

Tian

Chen

et al. 2020

J Orthop Surg Res

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Background: To study the effects of hypoxia and nutrition deficiency mimicking degenerated intervertebral disc on the biological behavior of human nucleus-derived pulposus mesenchymal stem cells (hNP-MSCs) and the role of PI3K/Akt pathway in the process in vitro. Methods: hP-MSCs were isolated from lumbar disc and were further identified by their immunophenotypes and multilineage differentiation. Then, cells were divided into the control group, hypoxia and nutrition deficiency group, the LY294002 group, and insulin-like growth factor 1 (IGF-1) group. Then cell apoptosis, the cell viability, the caspase 3 activity, and the expression of PI3K, Akt, and functional genes (aggrecan, collagen I, and collagen II) were evaluated. Result: Our work showed that isolated cells met the criteria of International Society for cellular Therapy. Therefore, cells obtained from degenerated nucleus pulposus were definitely hNP-MSCs. Our results showed that hypoxia and nutrition deficiency could significantly increase cell apoptosis, the caspase 3 activity, and inhibit cell viability. Gene expression results demonstrated that hypoxia and nutrition deficiency could increase the relative expression of PI3K and Akt gene and inhibit the expression of functional genes. However, when the PI3K/Akt pathway was inhibited by LY294002, the cell apoptosis and caspase 3 activity significantly increased while the cell viability was obviously inhibited. Quantitative real-time PCR results showed that the expression of functional genes was more significantly inhibited. Our study further verified that the abovementioned biological activities of hNP-MSCs could be significantly improved by IGF1. Conclusions: PI3K/Akt signal pathway may have protective effects on human nucleus pulposus-derived mesenchymal stem cells against hypoxia and nutrition deficiency.

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Biological Behavior of Human Nucleus Pulposus Mesenchymal Stem Cells in Response to Changes in the Acidic Environment During Intervertebral Disc Degeneration

Cited by 68 publications

References 43 publications

The effect of high glucose on the biological characteristics of nucleus pulposus‐derived mesenchymal stem cells

The effect of high glucose on the biological characteristics of nucleus pulposus‐derived mesenchymal stem cells

Mechanisms of endogenous repair failure during intervertebral disc degeneration

The protective effects of PI3K/Akt pathway on human nucleus pulposus mesenchymal stem cells against hypoxia and nutrition deficiency

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