Bone marrow-derived mesenchymal stem cell(MSC)is one of the most actively studied cell types due to its regenerative potential and immunomodulatory properties.Conventional cell expansion methods using 2D tissue cultur...Bone marrow-derived mesenchymal stem cell(MSC)is one of the most actively studied cell types due to its regenerative potential and immunomodulatory properties.Conventional cell expansion methods using 2D tissue culture plates and 2.5D microcarriers in bioreactors can generate large cell numbers,but they compromise stem cell potency and lack mechanical preconditioning to prepare MSC for physiological loading expected in vivo.To overcome these challenges,in this work,we describe a 3D dynamic hydrogel using magneto-stimulation for direct MSC manufacturing to therapy.With our technology,we found that dynamic mechanical stimulation(DMS)enhanced matrix-integrinβ1 interactions which induced MSCs spreading and proliferation.In addition,DMS could modulate MSC biofunctions including directing MSC differentiation into specific lineages and boosting paracrine activities(e.g.,growth factor secretion)through YAP nuclear localization and FAK-ERK pathway.With our magnetic hydrogel,complex procedures from MSC manufacturing to final clinical use,can be integrated into one single platform,and we believe this‘all-in-one’technology could offer a paradigm shift to existing standards in MSC therapy.展开更多
基金supported by NUS Presidential Young Professorship,MOE Tier 1 grantsupported by the NUS Research Scholarship.
文摘Bone marrow-derived mesenchymal stem cell(MSC)is one of the most actively studied cell types due to its regenerative potential and immunomodulatory properties.Conventional cell expansion methods using 2D tissue culture plates and 2.5D microcarriers in bioreactors can generate large cell numbers,but they compromise stem cell potency and lack mechanical preconditioning to prepare MSC for physiological loading expected in vivo.To overcome these challenges,in this work,we describe a 3D dynamic hydrogel using magneto-stimulation for direct MSC manufacturing to therapy.With our technology,we found that dynamic mechanical stimulation(DMS)enhanced matrix-integrinβ1 interactions which induced MSCs spreading and proliferation.In addition,DMS could modulate MSC biofunctions including directing MSC differentiation into specific lineages and boosting paracrine activities(e.g.,growth factor secretion)through YAP nuclear localization and FAK-ERK pathway.With our magnetic hydrogel,complex procedures from MSC manufacturing to final clinical use,can be integrated into one single platform,and we believe this‘all-in-one’technology could offer a paradigm shift to existing standards in MSC therapy.
