Mechano-responsive hydrogel for direct stem cell manufacturing to therapy

Abstract

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-integrin β1 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.

Graphical abstract

Highlights

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  Dynamic mechanical stimulation (DMS) induced by wireless magnetic field enhances matrix-integrin β1 interactions.

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  3D hydrogel platform optimizes mesenchymal stem cell (MSC) quantity and quality during manufacturing.

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  Mechanical pre-conditioning enhances MSC biofunctions including cell differentiation, expansion, and secretome.

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  ‘All-in-one’ strategy from MSC manufacturing to direct therapy/clinical use.