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,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~1800 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.展开更多
基金This work was supported by the National Key R&D Program[grant number 2019YFA0111900,to YJ],administered by the Ministry of Science and Technology of the People’s Republic of China(MOST,China)General Research Fund(GRF,grant number 14104022,to YJ)by Hong Kong Research Grants Council,University Grants Committee(RGC,UGC)of Hong Kong SAR,China+2 种基金The Chinese University of Hong Kong,Impact Postdoctoral Fellowship Scheme[IPDFS,CUHK,to JS]the Center for Neuromusculoskeletal Restorative Medicine[CNRM at InnoHK,to RST,YJ]by Innovation and Technology Commission(ITC)of Hong Kong SAR,ChinaLee Quo Wei and Lee Yick Hoi Lun Professorship in Tissue Engineering Regenerative Medicine of The Chinese University of Hong Kong(to RST).
文摘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~1800 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.
