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Review
. 2018 Jun 4:20:21-47.
doi: 10.1146/annurev-bioeng-062117-120954. Epub 2017 Dec 8.

Engineering Hydrogel Microenvironments to Recapitulate the Stem Cell Niche

Christopher M Madl  1 , Sarah C Heilshorn  2
Affiliations
Review

Engineering Hydrogel Microenvironments to Recapitulate the Stem Cell Niche

Christopher M Madl et al. Annu Rev Biomed Eng. .

Abstract

Stem cells are a powerful resource for many applications including regenerative medicine, patient-specific disease modeling, and toxicology screening. However, eliciting the desired behavior from stem cells, such as expansion in a naïve state or differentiation into a particular mature lineage, remains challenging. Drawing inspiration from the native stem cell niche, hydrogel platforms have been developed to regulate stem cell fate by controlling microenvironmental parameters including matrix mechanics, degradability, cell-adhesive ligand presentation, local microstructure, and cell-cell interactions. We survey techniques for modulating hydrogel properties and review the effects of microenvironmental parameters on maintaining stemness and controlling differentiation for a variety of stem cell types. Looking forward, we envision future hydrogel designs spanning a spectrum of complexity, ranging from simple, fully defined materials for industrial expansion of stem cells to complex, biomimetic systems for organotypic cell culture models.

Keywords: cell-adhesive ligands; cell–cell interactions; engineered cellular microenvironments; hydrogel; matrix mechanics; stem cell niche.

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Figures

Figure 1
Figure 1
Stem cell phenotypes and applications. Engineered hydrogels recapitulating aspects of the native stem cell niche can facilitate maintenance of stem cell quiescence, promote stem cell expansion, and direct stem cell differentiation. The stem cells and their differentiated progeny may be used for regenerative medicine applications, in vitro disease models, and toxicology screening.
Figure 2
Figure 2
Niche interactions known to modulate stem cell phenotype.
Figure 3
Figure 3
The spectrum of required simplicity/complexity for engineered hydrogel niches designed for future stem cell applications.
See this image and copyright information in PMC

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