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Evidence-Based Network Modelling to Simulate Nucleus Pulposus Multicellular Activity in Different Nutritional and

L Baumgartner1, A Sadowska2, L Tío3

  • 1BCN MedTech, Department of Information and Communication Technologies, Universitat Pompeu Fabra, Barcelona, Spain.

Frontiers in Bioengineering and Biotechnology
|December 3, 2021
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Summary
This summary is machine-generated.

This study models nucleus pulposus cell activity in response to biochemical stimuli, revealing TNF-α significantly drives degeneration. The integrated approach enhances understanding of intervertebral disc disease progression.

Keywords:
cell activityevidence-based simulationsin vitro experimentsinflammationintervertebral disc degenerationmulticellular systemsmultifactorial environmentnetwork modelling

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Area of Science:

  • Biomedical Engineering
  • Cellular Biology
  • Computational Biology

Background:

  • Intervertebral disc degeneration is a complex biological process influenced by biochemical and mechanical stimuli affecting cell activity.
  • Understanding how nucleus pulposus cells respond to a multifactorial environment of stimuli is crucial but remains unclear.
  • Existing research often examines individual stimuli, lacking insight into combined effects on cell behavior.

Purpose of the Study:

  • To develop an interdisciplinary approach combining experimental and in silico methods to model nucleus pulposus cell activity in multifactorial biochemical environments.
  • To investigate the impact of key stimuli (glucose, pH, TNF-α, IL1β) on specific cell activities, including mRNA expression of key genes.
  • To predict cell cluster behavior in different proinflammatory states within a multicellular 3D model.

Main Methods:

  • Developed a multicellular nucleus pulposus system model integrating in vitro experimental findings.
  • Utilized 3D cultures of bovine nucleus pulposus cells in alginate beads to determine unknown stimulus-cell activity relationships.
  • Employed a novel numerical approach to estimate cell activity sensitivity to individual stimuli and integrated these into a multifactorial model.

Main Results:

  • Glucose showed no significant impact on proinflammatory cytokine or ADAMTS4 mRNA expression.
  • Tumor Necrosis Factor-alpha (TNF-α) induced a significant catabolic shift in most explored cell activities.
  • The developed methodology for estimating cell activity sensitivity to stimuli improved qualitative model predictions.

Conclusions:

  • The integrated experimental and in silico approach provides a promising method for understanding nucleus pulposus cell responses in complex environments.
  • The study highlights TNF-α as a critical driver of catabolic changes in intervertebral disc cells.
  • Further integration of more stimuli, including mechanical loading, and experimental data is needed for more accurate predictions of disc degeneration progression.