An In Vitro Bioengineered Model of the Human Arterial Neurovascular Unit to Study Neurodegenerative Diseases
This week we profile a recent publication in Molecular Neurodegeneration
from the laboratory of Dr. Cheryl Wellington (pictured) at UBC.
Can you provide a brief overview of your lab’s current research focus?
My lab has a diverse portfolio of basic, translational and clinical projects, broadly organized into four major groups. The new Molecular Neurodegeneration paper focused on perfused engineered human brain tissues. We have embraced the field of tissue engineering and stem cells to create a highly innovative platform of 3-dimensional, perfusable functional human cerebral blood vessels fabricated from individual cellular components. We are working to develop a human-based “brain-in-a-bioreactor” platform that supports mechanistic studies relevant to multiple brain disorders. As we are particularly interested in the vascular contributions to Alzheimer’s disease, we absolutely need to have a “brain compartment” that is separated from a “blood compartment”, as standard approaches such as organoid culture are not perfusable. Our latest paper demonstrated that we can now integrate functional human induced pluripotent stem cell differentiated neurons to this platform and for the first time enabling electrophysiological experiments to be conducted in human neurons grown in a physiologically relevant 3D model of the neurovascular unit.
What is the significance of the findings in this publication?
The significance of the findings all stem from the bioreactor design of our system. Unlike many “chip”-based microfluidic models that are ideally positioned for drug discovery, our bioreactor platform is larger in scale and thus provides sufficient tissue for many kinds of experiments. In the Molecular Neurodegeneration paper, we provide proof-of-concept data that our approach may enable the kinds of studies in human neurons as are traditionally performed in mice, including studies of electrophysiology, synaptogenesis, neuronal degeneration, Alzheimer’s disease, and blood tests of neurological disorders.
What are the next steps for this research?
The next step in this research is to work with eminent engineers associated with UBC’s School of Biomedical Engineering to continue model development so that other labs can adopt and build on our technology. We are very fortunate to work with Dr. Karen Cheung and her remarkable team, who have already developed several upgrades to the bioreactor design to make this system more like a “kit” that we can share. We are also working on several projects related to understanding the vascular contributions to Alzheimer’s disease using this platform, where we can investigate brain factors, blood factors, and study their interactions. Some of these projects include amazing collaborators such as Dr. Haakon Nygaard of UBC, Dr. Guojun Bu of the Mayo Clinic, Dr. Alison Goate of the Icahn School of Medicine, and Dr. Li-Huei Tsai at Massachusetts Institute of Technology.
This work was funded by:
We are very grateful to the Cure Alzheimer’s Fund, the BrightFocus Foundation, the Weston Brain Institute, the UBC School of Biomedical Engineering, the Pacific Alzheimer’s Research Foundation, and several donors for supporting elements of this work. We are so grateful that you believed in our vision and provided the support to deliver on a very promising experimental platform.