ArticleStem cell research & therapy2024
Metabolic modulation to improve MSC expansion and therapeutic potential for articular cartilage repair.
Article in Stem cell research & therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 12 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
12 citing papers in PubMed.
- Multimodal Biophysical Analysis of Morpho-Phenotypic and Morpho-Functional Dynamics in Normal and Cancer Spheroids within Engineered Microenvironments.Chemical & biomedical imaging · 2026Article
- Article
- Recapitulating Endochondral Ossification for Bone Repair: From Development to Engineering Strategy.Advanced healthcare materials · 2026Review
- The Impact of Large-Scale Expansion on the Functional Properties of Mesenchymal Stem Cells.Stem cell reviews and reports · 2026Review
- Genomic analysis of dental pulp mesenchymal stromal cells for therapeutic applications.Regenerative therapy · 2026Article
- Cellular iron flux measurement by micromagnetic resonance relaxometry as a critical quality attribute of mesenchymal stromal cells.Stem cells translational medicine · 2026Article
- Insights into vitamin C in musculoskeletal physiology and disorders: mechanisms and translational perspectives.Frontiers in immunology · 2026Review
- Mesenchymal stem cell senescence as a potency brake: causes, consequences, and cures.Frontiers in aging · 2026Review
- Long-term evaluation of human iPSC-derived cartilage for repairing chondral defects.NPJ Regenerative medicine · 2025Article
- Effects of Different Forms of Selenium in Human Umbilical Cord Mesenchymal Stem Cells.Biomedicines · 2025Article
- Quality by design strategy of human mesenchymal stem/stromal cell drug products for the treatment of knee osteoarthritis.World journal of stem cells · 2025Review
- The Potential of Mesenchymal Stem Cells in Treating Spinocerebellar Ataxia: Advances and Future Directions.Biomedicines · 2024Review
Corrections and comments
- Erratum issued
Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundArticular cartilage degeneration can result from injury, age, or arthritis, causing significant joint pain and disability without surgical intervention. Currently, the only FDA cell-based therapy for articular cartilage injury is Autologous Chondrocyte Implantation (ACI); however, this procedure is costly, time-intensive, and requires multiple treatments. Mesenchymal stromal cells (MSCs) are an attractive alternative autologous therapy due to their availability and ability to robustly differentiate into chondrocytes for transplantation with good safety profiles. However, treatment outcomes are variable due to donor-to-donor variability as well as intrapopulation heterogeneity and unstandardized MSC manufacturing protocols. Process improvements that reduce cell heterogeneity while increasing donor cell numbers with improved chondrogenic potential during expansion culture are needed to realize the full potential of MSC therapy.
methodsIn this study, we investigated the potential of MSC metabolic modulation during expansion to enhance their chondrogenic commitment by varying the nutrient composition, including glucose, pyruvate, glutamine, and ascorbic acid in culture media. We tested the effect of metabolic modulation in short-term (one passage) and long-term (up to seven passages). We measured metabolic state, cell size, population doubling time, and senescence and employed novel tools including micro-magnetic resonance relaxometry (µMRR) relaxation time (T
resultsOur data show that the addition of 1 mM L-ascorbic acid-2-phosphate (AA) to cultures for one passage during MSC expansion prior to initiation of differentiation improves chondrogenic differentiation. We further demonstrate that AA treatment reduced the proportion of senescent cells and cell heterogeneity also allowing for long-term expansion that led to a > 300-fold increase in yield of MSCs with enhanced chondrogenic potential compared to untreated cells. AA-treated MSCs with improved chondrogenic potential showed a robust shift in metabolic profile to OXPHOS and higher µMRR T
conclusionsOur results suggest an improved MSC manufacturing process that can enhance chondrogenic potential by targeting MSC metabolism and integrating process analytic tools during expansion.
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