Mechano-responsive hydrogel for direct stem cell manufacturing to therapy

Yufeng Shou; Ling Liu; Qimin Liu; Zhicheng Le; Khang Leng Lee; Hua Li; Xianlei Li; Dion Zhanyun Koh; Yuwen Wang; Tong Ming Liu; Zheng Yang; Chwee Teck Lim; Christine Cheung; Andy Tay

doi:10.1016/j.bioactmat.2022.12.019

Mechano-responsive hydrogel for direct stem cell manufacturing to therapy

Bioact Mater. 2023 Jan 2:24:387-400. doi: 10.1016/j.bioactmat.2022.12.019. eCollection 2023 Jun.

Authors

Yufeng Shou^{1

2}, Ling Liu^{2

3}, Qimin Liu⁴, Zhicheng Le^{1

2}, Khang Leng Lee⁵, Hua Li⁶, Xianlei Li^{1

2}, Dion Zhanyun Koh¹, Yuwen Wang¹, Tong Ming Liu⁷, Zheng Yang^{3

8}, Chwee Teck Lim^{1

2

9}, Christine Cheung^{5

7}, Andy Tay^{1

2

3}

Affiliations

¹ Department of Biomedical Engineering, National University of Singapore, 117583, Singapore.
² Institute for Health Innovation & Technology, National University of Singapore, 117599, Singapore.
³ NUS Tissue Engineering Program, National University of Singapore, 117510, Singapore.
⁴ School of Civil Engineering and Architecture, Wuhan University of Technology, 430070, Wuhan, China.
⁵ Lee Kong Chian School of Medicine, Nanyang Technological University, 636921, Singapore.
⁶ School of Mechanical and Aerospace Engineering, Nanyang Technological University, 639798, Singapore.
⁷ Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (ASTAR), 138648, Singapore.
⁸ Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore, 119288, Singapore.
⁹ Mechanobiology Institute, National University of Singapore, 117411, Singapore.

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.

Keywords: Cell therapy; DMS, Dynamic Mechanical Stimulation; Dynamic mechanical stimulation; MP, Magnetic Particle; MSC, Mesenchymal Stem Cell; Magnetic hydrogel; Mesenchymal stem cell; Stem cell manufacturing.