Woodruff School of Mechanical Engineering
Mechanical Engineering Seminar
Directing Differentiation and Morphogenesis Via Engineering of Stem Cell Microenvironments
Dr. Todd C. McDevitt
Wallace H. Coulter Department of Biomedical Engineering, Georgia Tech
Tuesday, March 20, 2012 at 3:00:00 PM
MRDC Building, Room 4211
During the course of embryological development, stem cell differentiation and morphogenesis occur as a result of dynamic changes in the molecular composition and structure of the extracellular microenvironment. Thus, the development of approaches to systematically control biochemical and biophysical cues comprising the microenvironment of pluripotent and multipotent cells could facilitate an improved understanding of fundamental principles and mechanisms of stem cell and developmental biology. With this goal in mind, we have focused on spatially and temporally engineering the microenvironments of 3D stem cell aggregates to create robust and reproducible systems to investigate the dynamics of differentiation and morphogenesis 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; molecular analysis indicates that the hydrodynamic modulation of ESC phenotypes is mediated at least in part by temporal changes in intracellular β-catenin signaling. Furthermore, mechanical and physical characterization of differentiating EBs indicates global changes that accompany dynamic changes in cell phenotype and increasing transport limitations. 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. 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. Interestingly, the presence of different types of microparticles (of comparable size and incorporation density) also impacted cell phenotypes, however less so than morphogen-laden materials. Incorporation of paramagnetic microparticles within cell aggregates enabled non-contacxt 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 the combination of macro- and microscale enabling technologies can yield more effective and efficient routes to direct differentiation and morphogenesis of stem cells. In addition to yielding new insights into stem cell biology, these engineering-based strategies offer novel routes for stem cell tissue engineering and biomanufacturing.
Todd McDevitt, Ph.D. is an Associate Professor in the Wallace H. Coulter Department of Biomedical Engineering at the Georgia Institute of Technology and Emory University, and a Petit Faculty Fellow of the Parker H. Petit Institute for Bioengineering and Bioscience at Georgia Tech. In 2009, Dr. McDevitt was appointed the founding Director of the Stem Cell Engineering Center at Georgia Tech (http://scec.gatech.edu/). The McDevitt Laboratory for the Engineering of Stem Cell Technologies (http://mcdevitt.bme.gatech.edu/) is focused on developing enabling technologies for the directed differentiation and morphogenesis of stem cells for regenerative medicine therapies and in vitro diagnostic applications. Dr. McDevitt graduated cum laude with a Bachelor of Science in Engineering (B.S.E.) from Duke University in 1997 double majoring in Biomedical and Electrical Engineering and he received the Howard Clark Award for undergraduate research. He received his Ph.D. in Bioengineering from the University of Washington in 2001, and conducted post-doctoral research in the Department of Pathology at the University of Washington 2002-04.
Refreshments will be served.