"Slow walk" mimetic tensile loading maintains human meniscus tissue resident progenitor cells homeostasis in photocrosslinked gelatin hydrogel.
Bioact Mater
; 25: 256-272, 2023 Jul.
Article
em En
| MEDLINE
| ID: mdl-36825224
ABSTRACT
Meniscus, the cushion in knee joint, is a load-bearing tissue that transfers mechanical forces to extracellular matrix (ECM) and tissue resident cells. The mechanoresponse of human tissue resident stem/progenitor cells in meniscus (hMeSPCs) is significant to tissue homeostasis and regeneration but is not well understood. This study reports that a mild cyclic tensile loading regimen of â¼1800 loads/day on hMeSPCs seeded in 3-dimensional (3D) photocrosslinked gelatin methacryloyl (GelMA) hydrogel is critical in maintaining cellular homeostasis. Experimentally, a "slow walk" biomimetic cyclic loading regimen (10% tensile strain, 0.5 Hz, 1 h/day, up to 15 days) is applied to hMeSPCs encapsulated in GelMA hydrogel with a magnetic force-controlled loading actuator. The loading significantly increases cell differentiation and fibrocartilage-like ECM deposition without affecting cell viability. Transcriptomic analysis reveals 332 mechanoresponsive genes, clustered into cell senescence, mechanical sensitivity, and ECM dynamics, associated with interleukins, integrins, and collagens/matrix metalloproteinase pathways. The cell-GelMA constructs show active ECM remodeling, traced using a green fluorescence tagged (GFT)-GelMA hydrogel. Loading enhances nascent pericellular matrix production by the encapsulated hMeSPCs, which gradually compensates for the hydrogel loss in the cultures. These findings demonstrate the strong tissue-forming ability of hMeSPCs, and the importance of mechanical factors in maintaining meniscus homeostasis.
3D cell-based constructs; 3D, Three-dimensional; BMSCs, Bone marrow derived mesenchymal stem cells; Biomimetic cyclic loading; CFUs, Colony forming units; Col I, Collagen type I; Col II, Collagen type II; DS, Degree of substitution; ECM, Extracellular matrix; Extracellular matrix; GAGs, Glycosaminoglycans; GFT-GelMA, Green fluorescence-tagged GelMA; GelMA hydrogel; GelMA, Gelatin methacryloyl; Human meniscus progenitor cells; MeHA, Methacrylated hyaluronic acid; PCM, Pericellular matrix; PI, Propidium iodide; PPI, Protein-protein interaction; hMeSPCs, Human meniscus stem/progenitor cells
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Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article