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In silico modeling the potential clinical effect of growth factor treatment on the metabolism of human nucleus pulposus cells.
McDonnell, Emily E; Ní Néill, Tara; Wilson, Niamh; Darwish, Stacey L; Butler, Joseph S; Buckley, Conor T.
Afiliación
  • McDonnell EE; Trinity Centre for Biomedical Engineering, Trinity Biomedical Sciences Institute, Trinity College Dublin The University of Dublin Dublin Ireland.
  • Ní Néill T; Discipline of Mechanical, Manufacturing and Biomedical Engineering, School of Engineering, Trinity College Dublin The University of Dublin Dublin Ireland.
  • Wilson N; Trinity Centre for Biomedical Engineering, Trinity Biomedical Sciences Institute, Trinity College Dublin The University of Dublin Dublin Ireland.
  • Darwish SL; Discipline of Mechanical, Manufacturing and Biomedical Engineering, School of Engineering, Trinity College Dublin The University of Dublin Dublin Ireland.
  • Butler JS; Trinity Centre for Biomedical Engineering, Trinity Biomedical Sciences Institute, Trinity College Dublin The University of Dublin Dublin Ireland.
  • Buckley CT; Discipline of Mechanical, Manufacturing and Biomedical Engineering, School of Engineering, Trinity College Dublin The University of Dublin Dublin Ireland.
JOR Spine ; 7(3): e1352, 2024 Sep.
Article en En | MEDLINE | ID: mdl-39092165
ABSTRACT

Background:

While growth factors have the potential to halt degeneration and decrease inflammation in animal models, the literature investigating the effect of dosage on human cells is lacking. Moreover, despite the completion of clinical trials using growth differentiation factor-5 (GDF-5), no results have been publicly released.

Aims:

The overall objective was to quantitatively assess the effect of three clinically relevant concentrations of GDF-5 (0.25, 1, and 2 mg) as a therapeutic for disc regeneration. Materials and

methods:

Firstly, this work experimentally determined the effects of GDF-5 concentration on the metabolic and matrix synthesis rates of human nucleus pulposus (NP) cells. Secondly, in silico modeling was employed to predict the subsequent regenerative effect of different GDF-5 treatments (± cells).

Results:

This study suggests a trend of increased matrix synthesis with 0.25 and 1 mg of GDF-5. However, 2 mg of GDF-5 significantly upregulates oxygen consumption. Despite this, in silico models highlight the potential of growth factors in promoting matrix synthesis compared to cell-only treatments, without significantly perturbing the nutrient microenvironment.

Discussion:

This work elucidates the potential of GDF-5 on human NP cells. Although the results did not reveal statistical differences across all doses, the variability and response among donors is an interesting finding. It highlights the complexity of human response to biological treatments and reinforces the need for further human research and personalized approaches. Furthermore, this study raises a crucial question about whether these potential biologics are more regenerative in nature or better suited as prophylactic therapies for younger patient groups.

Conclusion:

Biological agents exhibit unique characteristics and features, demanding tailored development strategies and individualized assessments rather than a one-size-fits-all approach. Therefore, the journey to realizing the full potential of biological therapies is long and costly. Nonetheless, it holds the promise of revolutionizing spinal healthcare and improving the quality of life for patients suffering from discogenic back pain.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: JOR Spine Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: JOR Spine Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos