Abstract
BackgroundTo 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.MethodshP-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.ResultOur 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 above-mentioned biological activities of hNP-MSCs could be significantly improved by IGF1.ConclusionsPI3K/Akt signal pathway may have protective effects on human nucleus pulposus-derived mesenchymal stem cells against hypoxia and nutrition deficiency.
Highlights
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 and the role of phosphatidylinositol 3-kinase (PI3K)/Akt pathway in the process in vitro
Previous studies have confirmed that human degenerated and normal Intervertebral disc (IVD) contained human nucleus pulposusderived mesenchymal stem cells [6,7,8,9] and hNP-MSCs fulfilled morphological, immunophenotypic, and differentiation definition criteria described by the International Society of Cell Therapy for mesenchymal stromal cells
Afterwards, we investigated the effects of hypoxia and nutrition deficiency on the biological behavior of hNP-MSCs in vitro, and studied the role of PI3K/Akt signaling in the process
Summary
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. Exogenous mesenchymal stem cells (MSCs) have shown an ability to regenerate disc cells and maintain the normal structure of degenerated IVD [4]. Previous studies have confirmed that human degenerated and normal IVD contained human nucleus pulposusderived mesenchymal stem cells (hNP-MSCs) [6,7,8,9] and hNP-MSCs fulfilled morphological, immunophenotypic, and differentiation definition criteria described by the International Society of Cell Therapy for mesenchymal stromal cells. These cells could retard the process of IVD degeneration [10]. It is hard to maintain the number of the active hNP-MSCs under the adverse microenvironment in the degenerated IVD and leads to repair failure of endogenous hNP-MSCs [11]
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