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Mechano-Hypoxia Conditioning of Engineered Human Meniscus

ABSTRACT: Mechano-Hypoxia Conditioning of Engineered Human Meniscus

PROVIDER: PRJNA748371 | ENA |

REPOSITORIES: ENA

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Mechano-Hypoxia Conditioning of Engineered Human Meniscus

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

Mechano-Hypoxia Conditioning of Engineered Human Meniscus.

Project description: Not available

| S-EPMC8446439 | biostudies-literature

Human engineered meniscus transcriptome after short-term combined hypoxia and dynamic compression

Project description:Human engineered meniscus transcriptome after short-term combined hypoxia and dynamic compression

| PRJNA702277 | ENA

Human engineered meniscus transcriptome after short-term combined hypoxia and dynamic compression

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

Engineered human meniscus in modeling sex differences of knee osteoarthritis in vitro

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

Mechanical Unloading of Engineered Human Meniscus Models Under Simulated Microgravity

Project description:Mechanical Unloading of Engineered Human Meniscus Models Under Simulated Microgravity

| PRJNA794056 | ENA

Mechano-hypoxia conditioning with TGF-β3 withdrawal promotes stable, non-hypertrophic chondrogenesis of human mesenchymal stem cells

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

Engineered human meniscus in modeling sex differences of knee osteoarthritis in vitro

Project description:Engineered human meniscus in modeling sex differences of knee osteoarthritis in vitro

| PRJNA794057 | ENA

Single cell-seq identify discoid lateral meniscus

Project description:Discoid lateral meniscus (DLM) is more prone to injury than a normally shaped meniscus. Our previous study successfully identified the different cell types and their corresponding marker genes in meniscus tissues, but there was no study comparing the gene expression and cell heterogenicity of discoid meniscus with normal meniscus.

2023-12-06 | GSE162767 | GEO

Gene signature of the embryonic meniscus

Project description:Analysis of gene expression in E16 mouse meniscus, articular cartilage, and cruciate ligaments Limbs were dissected from E16 CD-1 mice. Samples were frozen in OCT and cryosectioned. Meniscus, articular carilage, and cruciate ligament were isolated using laser capture microdissection. Total RNA was isolated from these tissues, amplified, and gene expression was analyzed using microarrays. Three biological replicates were analyzed for each tissue type. Total RNA extracted from E16 mouse meniscus, articular cartilage, and cruciate ligaments

2013-10-01 | E-GEOD-47799 | biostudies-arrayexpress

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