Randolph S. Ashton received his B.S. from Hampton University (Hampton, Virginia, 2002) and Ph.D. from Rensselaer Polytechnic Institute (Troy, NY, 2007) in Chemical Engineering. During graduate studies under Prof. Ravi Kane, he researched how engineering biomaterials at the nanoscale could regulate the fate of adult neural stem cells. He continued to pursue his interest in stems cells and tissue engineering as a California Institute for Regenerative Medicine and a NIH postdoctoral fellow at the University of California Berkeley’s Stem Cell Center in the lab of Prof. David Schaffer. In 2011, he was appointed to a faculty position in the Wisconsin Institute for Discovery at the University of Wisconsin Madison as an Assistant Professor of Biomedical Engineering. The goal of Dr. Ashton’s research is to provide novel regenerative therapies to treat CNS diseases and injury. His lab is currently developing scalable protocols to generate region-specific central nervous system tissues from human pluripotent stem cells (hPSCs). They also meld state of the art biomaterial approaches with hPSC-derived neural stem cells to engineer brain and spinal cord tissue models in vitro. Among his awards and honors, Dr. Ashton was named a 2015 Emerging Investigator by Chemical Communications and a 2013 Rising Star by the Biomedical Engineering Society’s Cellular and Molecular Bioengineering Special Interest Group. Also, he has been awarded a Burroughs Wellcome Fund Innovation in Regulatory Science Award, a Draper Technology Innovation Award from the Wisconsin Alumni Research Foundation, a Basic Research Award from the UW Institute for Clinical & Translational Research, and research grants from the NIH and EPA.
Title of Abstract
Human pluripotent stem cell (hPSC) derived neural organoids provide unprecedented potential to recapitulate human brain and spinal cord tissues in vitro. However, organoid morphogenesis relies upon spontaneous emergence of biomimetic tissue structures in the absence of normal developmental constraints and morphogen signaling centers. This inherently limits the reproducibility and biomimicry of organoid cytoarchitecture and potentially impedes maturation and interconnectivity of developing tissue structures. As an initial step in overcoming these limitations, we have begun investigating how spatial and temporal control of tissue morphology and morphogen gradients can be used to instruct controlled neural organoid morphogenesis in 2- and 3D. Using micropatterned culture of hPSC-derived neural stem cells (NSCs), we have identified biophysical parameters necessary to induce the emergence of tissues with a singular neural rosette cytoarchitecture (>80% efficiency), which resembles a 2D cross-section of the developing neural tube. Additionally, we are (1) applying microfluidic morphogen gradients to pattern ventral thru dorsal progenitor domains within arrayed neural rosette tissues, and (2) have engineered culture substrates that enable spatiotemporal control of the tissues’ radial expansion while maintaining an apical, polarized neuroepithelial zone. Similar concepts are also being applied in 3D to generate biomimetic human neural tube analogs using a sacrificial lattice biomaterial platform. Ultimately, we aim to meld engineered culture platforms and organoid derivation protocols to enable reproducible derivation of brain and spinal cord tissues with organotypic cell phenotype diversity and biomimetic cytoarchitecture.
Gavin T Knight (1,2), Carlos Marti-Figueroa (1,2), Nisha Iyer (2), Brady S Lundin (1,2), Frank Seipel (1,2), Stephanie Cuskey (2), and Randolph S Ashton (1,2)
All Author Affiliations
(1) Department of Biomedical Engineering, University of Wisconsin, Madison WI, USA
(2) Wisconsin Institute for Discovery, University of Wisconsin, Madison WI, USA