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Updated: Jun 26, 2026

Optical Sectioning and Visualization of the Intervertebral Disc from Embryonic Development to Degeneration
Published on: July 8, 2021
MSC response to pH levels found in degenerating intervertebral discs
Karin Wuertz1, Karolyn Godburn, James C Iatridis
1School of Engineering, University of Vermont, Burlington, Vermont, USA. wuertz@cabmm.uzh.ch
Abstract:
Painful degenerative disc disease is a major health problem and for successful tissue regeneration, MSCs must endure and thrive in a harsh disc microenvironment that includes matrix acidity as a critical factor. MSCs were isolated from bone marrow of Sprague-Dawley rats from two different age groups (<1 month, n=6 and 4-5 months, n=6) and cultured under four different pH conditions representative of the healthy, mildly or severely degenerated intervertebral disc (pH 7.4, 7.1, 6.8, and 6.5) for 5 days. Acidity caused an inhibition of aggrecan, collagen-1, and TIMP-3 expression, as well as a decrease in proliferation and viability and was associated with a change in cell morphology. Ageing had generally minor effects but young MSCs maintained greater mRNA expression levels. As acidic pH levels are typical of increasingly degenerated discs, our findings demonstrate the importance of early interventions and predifferentiation when planning to use MSCs for reparative treatments.
Insights
Tissue regeneration using mesenchymal stem cells (MSCs) is hindered by acidic conditions in degenerated discs. Early intervention and predifferentiation are crucial for successful MSC-based therapies in degenerative disc disease.
Area of Science:
- Biomedical Engineering
- Regenerative Medicine
- Cell Biology
Background:
- Degenerative disc disease (DDD) is a significant health issue.
- Mesenchymal stem cells (MSCs) are crucial for tissue regeneration.
- The disc microenvironment, particularly matrix acidity, poses challenges for MSC survival and function.
Purpose of the Study:
- To investigate the impact of varying pH levels, simulating disc degeneration, on rat bone marrow-derived MSCs.
- To assess the effects of acidity and age on MSC gene expression, proliferation, viability, and morphology.
Main Methods:
- MSCs were isolated from young (<1 month) and adult (4-5 months) Sprague-Dawley rats.
- Cells were cultured for 5 days at four different pH conditions (7.4, 7.1, 6.8, 6.5).
- Gene expression (aggrecan, collagen-1, TIMP-3), proliferation, viability, and cell morphology were analyzed.
Main Results:
- Acidity significantly inhibited aggrecan, collagen-1, and TIMP-3 expression.
- Lower pH levels led to decreased MSC proliferation and viability.
- Cell morphology changed under acidic conditions, with younger MSCs showing higher mRNA expression levels.
Conclusions:
- Acidic conditions, characteristic of degenerated discs, impair MSC function and viability.
- Age influences MSC response, with younger cells exhibiting better mRNA expression.
- Findings highlight the necessity of early therapeutic interventions and MSC predifferentiation for effective DDD treatment.
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