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A research team led by UHN's Dr. Blair Gage has generated functional blood vessel cells found in the liver from stem cells, a discovery that offers an unprecedented opportunity to study in detail the role these cells play in liver development and disease progression, and which could lead to new therapies to treat hemophilia A.
"By combining insights from developmental biology and liver anatomy with the cell atlas of the human liver, we were able to generate and validate functional human liver vasculature from stem cells," says Dr. Gage, a post-doctoral fellow at the McEwen Stem Cell Institute at UHN, and lead author of the study.
"Now we can move forward to use these liver endothelial cells to better understand their role in liver function and to develop new therapies to treat disorders such as hemophilia A."
The study, titled "Generation of Functional Liver Sinusoidal Endothelial Cells from Human Pluripotent Stem Cell-Derived Venous Angioblasts," was published on July 7 in
Cell Stem Cell. The research was done in the laboratory of Dr. Gordon Keller, Director and Senior Scientist at the McEwen Stem Cell Institute at UHN.
It represents a collaborative effort between basic and clinical researchers at UHN and the University of Toronto (U of T), with expertise in stem cell and computational biology, human liver physiology and function, and liver transplantation. The team is funded by U of T's Medicine by Design.
The interdisciplinary research team also includes: Jeff C. Liu, research associate at the Donnelly Centre for Cellular and Biomolecular Research at U of T; Brendan T. Innes, PhD candidate at the Donnelly Centre and the Department of Molecular Genetics at U of T; Dr. Sonya A. MacParland, scientist at the Soham & Shaila Ajmera Family Transplant Centre, Toronto General Hospital Research Institute, and assistant professor in the departments of Immunology and Laboratory Medicine and Pathobiology at U of T; Dr. Ian D. McGilvray, Senior Scientist at the Soham & Shaila Ajmera Family Transplant Centre, Toronto General Hospital Research Institute, and professor at the Department of General Surgery at U of T; Dr. Gary D. Bader, professor at the Donnelly Centre and the Department of Molecular Genetics at U of T; and Dr. Keller, who is also professor at the Department of Medical Biophysics at U of T.
This research was supported by U of T’s Medicine by Design, which receives funding from the federal government’s Canada First Research Excellence Fund, and by the Canadian Institutes of Health Research.