Drug Discovery 2022: driving the next life science revolution

Novel 3D Hydrogel System Enhances Regenerative Capacity of Stem Cells and Improves Tailorability of Biologics


J Hodge1; A Mellott2; A Sim3; A Amari3
1 University of Kansas, United States;  2 Ronawk, United States;  3 AMS Biotechnology (Europe), UK


2D culture plastic is suboptimal for cell expansion, particularly “stem-like” cells like MSCs, and can cause loss of multipotency, induction of senescence, and decreased bioactivity. MSC-derived therapies are promising, but the use of standard 2D culture techniques is a limitation to therapeutic efficacy. We developed a modular 3D system with tailorable properties to generate a system that improves MSC viability and “stem-like” phenotypic characteristics in culture, resulting in more effective therapeutics. Human MSCs were expanded in either 2D culture or a novel 3D system. The 3D system is a customizable bioprinted hydrogel, formulated to mimic the native soft tissue of origin for specific cell populations, including bioinert and bioactively modified formulations. The 3D system contains a microarchitectural design that promotes cell migration and proliferation and eliminates the need to subculture cells. Culture of MSCs within the bioinert 3D system allowed direct observation of the effects of 3D culture and substrate mechanics on MSC functionality, without using bioactive modulators. Our data demonstrated a significant reduction in senescence and increased expression of “stem-like” markers in MSC populations within the 3D system. Proteomic evaluation of the Conditioned Media (CM) indicated that 3D expansion significantly increased secretion of regenerative factors. Similarly, co-culture of a secondary cell population with CM demonstrated significant enhancement of cell proliferation, migration, and metabolic activity when treated with MSC-CM from 3D relative to 2D. Subsequently, culture of MSCs within the bioactively modified 3D system resulted in MSC-CM that further augmented the proliferation, migration, and metabolic activity of the secondary cell population, relative to the 3D system. This demonstrates the potential of a novel 3D system to enhance the regenerative capacity of MSCs, with capability to tailor MSC-derived biologics.

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