Hydrogels for Large-Scale Expansion of Stem Cells

Stem cells demonstrate considerable promise for various preclinical and clinical applications, including drug screening, disease treatments, and regenerative medicine. Producing high-quality and large amounts of stem cells is in demand for these applications. Despite challenges, as hydrogel-based cell culture technology has developed, tremendous progress has been made in stem cell expansion and directed differentiation. Hydrogels are soft materials with abundant water. Many hydrogel properties, including biodegradability, mechanical strength, and porosity, have been shown to play essential roles in regulating stem cell proliferation and differentiation. The biochemical and physical properties of hydrogels can be specifically tailored to mimic the native microenvironment that various stem cells reside in vivo. A few hydrogel-based systems have been developed for successful stem cell cultures and expansion in vitro. In this review, we summarize various types of hydrogels that have been designed to effectively enhance the proliferation of hematopoietic stem cells (HSCs), mesenchymal stem/stromal cells (MSCs), and pluripotent stem cells (PSCs), respectively. According to each stem cell type's preference, we also discuss strategies for fabricating hydrogels with biochemical and mechanical cues and other characteristics representing microenvironments of stem cells in vivo. In this review article we summarize current progress on the construction of hydrogel systems for the culture and expansion of various stem cells, including hematopoietic stem cells (HSCs), mesenchymal stem/stromal cells (MSCs), and pluripotent stem cells (PSCs). The Significance includes: (1) Provide detailed discussion on the stem cell niches that should be considered for stem cell in vitro expansion. (2) Summarize various strategies to construct hydrogels that can largely recapture the microenvironment of native stem cells. (3) Suggest a few future directions that can be implemented to improve current in vitro stem cell expansion systems.