@article {1576533,
	title = {Multifunctional biomimetic hydrogel systems to boost the immunomodulatory potential of mesenchymal stromal cells},
	journal = {Biomaterials},
	volume = {257},
	year = {2020},
	month = {2020 10},
	pages = {120266},
	abstract = {Mesenchymal stromal cells (MSCs) hold great therapeutic potential, in part because of their immunomodulatory properties. However, these properties can be transient and depend on multiple factors. Here, we developed a multifunctional hydrogel system to synergistically enhance the immunomodulatory properties of MSCs, using a combination of sustained inflammatory licensing and three-dimensional (3D) encapsulation in hydrogels with tunable mechanical properties. The immunomodulatory extracellular matrix hydrogels (iECM) consist of an interpenetrating network of click functionalized-alginate and fibrillar collagen, in which interferon γ (IFN-γ) loaded heparin-coated beads are incorporated. The 3D microenvironment significantly enhanced the expression of a wide panel of pivotal immunomodulatory genes in bone marrow-derived primary human MSCs (hMSCs), compared to two-dimensional (2D) tissue culture. Moreover, the inclusion of IFN-γ loaded heparin-coated beads prolonged the expression of key regulatory genes upregulated upon licensing, including indoleamine 2,3-dioxygenase 1 (IDO1) and galectin-9 (GAL9). At a protein level, iECM hydrogels enhanced the secretion of the licensing responsive factor Gal-9 by hMSCs. Its presence in hydrogel conditioned media confirmed the correct release and diffusion of the factors secreted by hMSCs from the system. Furthermore, co-culture of iECM-encapsulated hMSCs and activated human T cells resulted in suppressed proliferation, demonstrating direct regulation on immune cells. These data highlight the potential of iECM hydrogels to enhance the immunomodulatory properties of hMSCs in cell therapies.},
	keywords = {Biomimetics, Culture Media, Conditioned, Humans, Hydrogels, Immunomodulation, Mesenchymal Stem Cells},
	issn = {1878-5905},
	doi = {10.1016/j.biomaterials.2020.120266},
	author = {Gonzalez-Pujana, Ainhoa and Vining, Kyle H and Zhang, David K Y and Santos-Vizcaino, Edorta and Igartua, Manoli and Hernandez, Rosa Maria and Mooney, David J}
}
