Proteolytically degradable microparticles for engineering the extracellular microenvironment of pluripotent stem cell aggregates

Gelatin methacrylate;Microparticles;Pluripotent;Stem cells;Differentiation

Nguyen, Anh H. ; McDevitt, Todd C. Biomedical Engineering (Joint GT/Emory Department) García, Andrés J. Platt, Manu Barker, Thomas Xu, Chunhui ; McDevitt, Todd C.

University:Georgia Institute of Technology

Department:Biomedical Engineering (Joint GT/Emory Department)

关键词: Gelatin methacrylate;    Microparticles;    Pluripotent;    Stem cells;    Differentiation;   

Others  :  https://smartech.gatech.edu/bitstream/1853/54845/1/NGUYEN-DISSERTATION-2015.pdf

美国|英语

来源: SMARTech Repository

【 摘 要 】

During embryo development, extracellular matrix (ECM) remodeling by matrix metalloproteinases (MMPs) and promotes downstream cell specifications. Pluripotent stem cell (PSC) aggregates can recapitulate various aspects of embryogenesis in vitro, and incorporation of biomaterial microparticles also provides an ideal platform to study cell-biomaterial interactions. Stem cell interactions with ECM-based biomaterials can impact tissue remodeling and differentiation propensity via modulation of MMP activity. This work investigated the MMP activity and subsequent mesenchymal differentiation of embryonic stem cell (ESC) aggregates with incorporated gelatin methacrylate (GMA) MPs with either low (20%) or high (90%) cross-linking densities, corresponding to faster or slower degradation rate, respectively. GMA MP incorporation increased total MMP and MMP-2 levels within 3D ESC aggregates in a substrate-dependent manner. GMA MP-incorporated aggregates also expressed higher levels of epithelial-to-mesenchymal transition markers and displayed enhanced mesenchymal morphogenesis than aggregates without MPs, and the MP-mediated effects were completely abrogated with MMP inhibitor treatment. This work predicts that control of proteolytic responses via introducing ECM-based MPs may offer a novel avenue to engineer the ECM microenvironment to modulate stem cell differentiation.