Organotypic Cultures of Intervertebral Disc Cells: Responses to Growth Factors and Signaling Pathways Involved

Overview

Journal Biomed Res Int

Publisher Wiley

Specialties Biomedical Engineering
Biotechnology
General Medicine

Date 2015 Nov 20

PMID 26583105

Citations 6

Authors

Harris Pratsinis

Dimitris Kletsas

Affiliations

Soon will be listed here.

Abstract

Intervertebral disc (IVD) degeneration is strongly associated with low back pain, a major cause of disability worldwide. An in-depth understanding of IVD cell physiology is required for the design of novel regenerative therapies. Accordingly, aim of this work was the study of IVD cell responses to mitogenic growth factors in a three-dimensional (3D) organotypic milieu, comprising characteristic molecules of IVD's extracellular matrix. In particular, annulus fibrosus (AF) cells were cultured inside collagen type-I gels, while nucleus pulposus (NP) cells in chondroitin sulfate A (CSA) supplemented collagen gels, and the effects of Platelet-Derived Growth Factor (PDGF), basic Fibroblast Growth Factor (bFGF), and Insulin-Like Growth Factor-I (IGF-I) were assessed. All three growth factors stimulated DNA synthesis in both AF and NP 3D cell cultures, with potencies similar to those observed previously in monolayers. CSA supplementation inhibited basal DNA synthesis rates, without affecting the response to growth factors. ERK and Akt were found to be phosphorylated following growth factor stimulation. Blockade of these two signaling pathways using pharmacologic inhibitors significantly, though not completely, inhibited growth factor-induced DNA synthesis. The proposed culture systems may prove useful for further in vitro studies aiming at future interventions for IVD regeneration.

Citing Articles

Signaling Mechanisms of Stem Cell Therapy for Intervertebral Disc Degeneration.

Du X, Liang K, Ding S, Shi H Biomedicines. 2023; 11(9).

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Platelet-Derived Growth Factor-BB Inhibits Intervertebral Disc Degeneration via Suppressing Pyroptosis and Activating the MAPK Signaling Pathway.

Zhang W, Gong Y, Zheng X, Qiu J, Jiang T, Chen L Front Pharmacol. 2022; 12:799130.

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Suramin attenuates intervertebral disc degeneration by inhibiting NF-κB signalling pathway.

Liu Z, Lu C, Shen P, Chou S, Shih C, Chen J Bone Joint Res. 2021; 10(8):498-513.

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Effect of Whole Tissue Culture and Basic Fibroblast Growth Factor on Maintenance of Tie2 Molecule Expression in Human Nucleus Pulposus Cells.

Sako K, Sakai D, Nakamura Y, Schol J, Matsushita E, Warita T Int J Mol Sci. 2021; 22(9).

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The effects of 3D culture on the expansion and maintenance of nucleus pulposus progenitor cell multipotency.

Guerrero J, Hackel S, Croft A, Albers C, Gantenbein B JOR Spine. 2021; 4(1):e1131.

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