Seminar Series: Todd McDevitt,Phd (Georgia Tech)" Engineering 3D stem cell microenvironments to direct differentiation and promote morphogenesis"
Science / Technology - Lecture/Discussion - WPI Only
Wednesday, September 26, 2012
4:00 PM-5:00 PM
Stem cell fate decisions are regulated by the combination of exogenous and endogenous signals that constitute the biochemical and biophysical properties of the extracellular microenvironment. Thus, in order to better understand and ultimately control differentiation and morphogenesis, we have focused on systematically engineering global and local elements of the 3D microenvironments of stem cells to create robust and reproducible systems to investigate the dynamics of stem cell biology in vitro. For example, macroscopic hydrodynamic forces (imparted by rotary orbital suspension culture) enhance the efficiency, yield and homogeneity of pluripotent embryonic stem cell (ESC) spheroids referred to as “embryoid bodies” (EB). Moreover, hydrodynamic conditions impact global transcriptional activity and subsequent differentiation of EB cell populations to different germ lineages, and the hydrodynamic modulation of ESC phenotypes is mediated at least in part by temporal changes in intracellular β-catenin signaling. As the cells within EBs begin to differentiate, they also start to undergo morphogenic processes due to extracellular matrix deposition and multicellular remodeling that manifest as mechanical property changes of individual aggregates, thus allowing for a novel means of non-destructively monitoring differentiation. In order to locally control the biochemical milieu of the microenvironment within 3D multicellular aggregates, microparticles of different materials were physically entrapped in stem cell spheroids without adversely affecting cell viability or intercellular adhesion. Interestingly, the presence of different types of microparticles alone (PLGA, agarose, gelatin) could significantly alter gene expression profiles and the spatial organization of different cell phenotypes within EBs. Presentation of morphogenic factors, such as retinoic acid and bone morphogenic protein-4, from microparticles induced gross morphological and phenotypic differences in the spatial and temporal patterning of ESC fates compared to soluble delivery methods. Incorporation of paramagnetic microparticles within cell aggregates enabled external manipulation of spheroid populations via magnetic forces and the spatial patterning of complex multicellular structures. Altogether, these results demonstrate that regulating stem cell 3D environments via macro- and microscale technologies yields inherently scalable routes to direct differentiation and morphogenesis in suspension culture systems, thereby benefitting the development of regenerative cellular therapies, in vitro cell based diagnostic technologies, and the engineering of tissues directly from stem cells.
Suggested Audiences: Adult, College
Last Modified: September 10, 2012 at 2:09 PM