Mechano-Hypoxia Conditioning of Engineered Human Meniscus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA748371 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR15197948_1.fastq.gz | Fastqsanger.gz | |||
| SRR15197948_2.fastq.gz | Fastqsanger.gz | |||
| SRR15197949_1.fastq.gz | Fastqsanger.gz | |||
| SRR15197949_2.fastq.gz | Fastqsanger.gz | |||
| SRR15197950_1.fastq.gz | Fastqsanger.gz |
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Project description:Meniscus fibrochondrocytes (MFCs) experience simultaneous hypoxia and mechanical loading in the knee, conditions that have promising applications in human meniscus tissue engineering. We hypothesized that “mechano-hypoxia conditioning,” using mechanical loading such as dynamic compression (DC) and cyclic hydrostatic pressure (CHP), would enhance development of human meniscus fibrocartilage extracellular matrix in vitro. MFCs from inner human meniscus surgical discards were pre-cultured on porous type I collagen scaffolds with TGF-β3 supplementation to form baseline tissues with newly-formed matrix. They were then treated with DC or CHP under hypoxia (HYP, 3% O2) for 5 days. DC was the more effective load regime, and combined HYP/DC enhanced gene expression of fibrocartilage precursors. The individual treatments of DC and HYP regulated thousands of genes and combined in an overwhelmingly additive rather than synergistic manner. Baseline tissues were then treated with a short course of DC (5 vs 60 minutes, 10-20% vs 30-40% strain) with different pre-culture durations (3 vs 6 weeks). Longer courses of loading had diminishing returns in terms of gene regulation. There was a dose-effect for higher DC strains, whereas outcomes were mixed for different MFC donors in pre-culture durations. Finally, baseline tissues were conditioned for 3 weeks with mechano-hypoxia conditioning to assess mechanical and protein-level outcomes. There were 1.8 to 5.1-fold gains in the dynamic modulus relative to baseline in HYP/DC, but matrix outcomes were equal or inferior to static controls. Long-term mechano-hypoxia conditioning was effective in suppressing hypertrophic markers (e.g., COL10A1 10-fold suppression vs static/normoxia). Applied appropriately, mechano-hypoxia conditioning can support meniscus fibrocartilage development in vitro and may be useful as a strategy for developing non-hypertrophic articular cartilage using mesenchymal stem cells.
2021-08-23 | GSE180467 | GEO
Project description:Meniscus fibrochondrocytes (MFCs) experience simultaneous hypoxia and mechanical loading in the knee joint. Experimental conditions based on these aspects of the native MFC environment may have promising applications in human meniscus tissue engineering. We hypothesized that in vitro "mechano-hypoxia conditioning" with mechanical loading such as dynamic compression (DC) and cyclic hydrostatic pressure (CHP) would enhance development of human meniscus fibrocartilage extracellular matrix in vitro. MFCs from inner human meniscus surgical discards were pre-cultured on porous type I collagen scaffolds with TGF-β3 supplementation to form baseline tissues with newly formed matrix that were used in a series of experiments. First, baseline tissues were treated with DC or CHP under hypoxia (HYP, 3% O2) for 5 days. DC was the more effective load regime in inducing gene expression changes, and combined HYP/DC enhanced gene expression of fibrocartilage precursors. The individual treatments of DC and HYP regulated thousands of genes, such as chondrogenic markers SOX5/6, in an overwhelmingly additive rather than synergistic manner. Similar baseline tissues were then treated with a short course of DC (5 vs 60 min, 10-20% vs 30-40% strain) with different pre-culture duration (3 vs 6 weeks). The longer course of loading (60 min) had diminishing returns in regulating mechano-sensitive and inflammatory genes such as c-FOS and PTGS2, suggesting that as few as 5 min of DC was adequate. There was a dose-effect in gene regulation by higher DC strains, whereas outcomes were inconsistent for different MFC donors in pre-culture durations. A final set of baseline tissues was then cultured for 3 weeks with mechano-hypoxia conditioning to assess mechanical and protein-level outcomes. There were 1.8-5.1-fold gains in the dynamic modulus relative to baseline in HYP/DC, but matrix outcomes were equal or inferior to static controls. Long-term mechano-hypoxia conditioning was effective in suppressing hypertrophic markers (e.g., COL10A1 10-fold suppression vs static/normoxia). Taken together, these results indicate that appropriately applied mechano-hypoxia conditioning can support meniscus fibrocartilage development in vitro and may be useful as a strategy for developing non-hypertrophic articular cartilage using mesenchymal stem cells.
| S-EPMC8446439 | biostudies-literature
Project description:Human engineered meniscus transcriptome after short-term combined hypoxia and dynamic compression
| PRJNA702277 | ENA
Project description:This study investigates the transcriptome response of meniscus fibrochondrocytes (MFCs) to the low oxygen and mechanical loading signals experienced in the knee joint using a model system. We hypothesized that short term exposure to the combined treatment would promote a matrix-forming phenotype supportive of inner meniscus tissue formation. Human MFCs on a collagen scaffold were stimulated to form fibrocartilage over 6weeks under normoxic (NRX, 20% O2) conditions with supplemented TGF -β3. Tissues experienced a delayed 24h hypoxia treatment (HYP, 3% O2) and then 5min of dynamic compression (DC) between 30 and 40% strain. Delayed HYP induced an anabolic and anti-catabolic expression profile for hyaline cartilage matrix markers, while DC induced an inflammatory matrix remodeling response along with upregulation of both SOX9 and COL1A1. There were 41 genes regulated by both HYP and DC. Overall, the combined treatment supported a unique gene expression profile favouring the hyaline cartilage aspect of inner meniscus matrix and matrix remodeling.
2021-02-17 | GSE166908 | GEO
Project description:Mechano-hypoxia conditioning with TGF-β3 withdrawal promotes stable, non-hypertrophic chondrogenesis of human mesenchymal stem cells
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Project description:This study aimed to evaluate the effects of mechanical loading and unloading via CHP and SMG, respectively, on the OA-related profile changes of engineered meniscus tissues and explore biological sex-related differences
2022-01-26 | GSE192982 | GEO
Project description:Mechanical Unloading of Engineered Human Meniscus Models Under Simulated Microgravity
| PRJNA794056 | ENA
Project description:We hypothesize that the combination of mechanical loading with hypoxia culture and TGF-β3 growth factor withdrawal will promote stable, non-hypertrophic chondrogenesis of hBM-MSC embedded in an HA-hydrogel. To this end, we first assessed static hypoxia culture with growth factor withdrawal against static normoxia (20% O2) culture at the global transcriptome and tissue matrix level. We then assess two modalities of mechanical loading (dynamic compression, DC and cyclic hydrostatic pressure, CHP) with growth factor withdrawal against static culture, all under hypoxia. Results showed that Mechanical stimulation and TGF-β3 withdrawal under hypoxia promoted a strong chondrogenic and non-hypertrophic phenotype of hBM-MSC.
2023-04-19 | GSE214720 | GEO
Project description:Meniscus injuries are common and while surgical strategies have improved, there is a need for alternative therapeutics to improve long-term outcomes and prevent post-traumatic osteoarthritis. Current research efforts in regenerative therapies and tissue engineering are hindered by a lack of understanding of meniscus cell biology and a poorly defined meniscus cell phenotype. This study utilized bulk RNA-sequencing to identify unique and overlapping transcriptomic profiles in cartilage, inner and outer zone meniscus tissue, and passaged inner and outer zone meniscus cells. The greatest transcriptomic differences were identified when comparing meniscus tissue to monolayer cultured cells (> 4,600 differentially expressed genes (DEGs)) and meniscus tissue to cartilage (> 3,100 DEGs). While zonal differences exist within the meniscus tissue (205 DEGs between inner and outer zone meniscus tissue), meniscus resident cells are more similar to each other than to either cartilage or monolayer meniscus cells. Additionally, we identified and validated LUM and PRRX1 as potential markers for meniscus tissue and ACTA2, FSTL1, SFRP2, and TAGLN as novel markers for meniscus cell dedifferentiation. Our data contribute significantly to the current characterization of meniscus cells and provide an important foundation for future work in meniscus cell biology, regenerative medicine, and tissue engineering.
2024-11-10 | GSE275100 | GEO
Project description:Engineered human meniscus in modeling sex differences of knee osteoarthritis in vitro
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