We explore what makes the cells that line your blood vessels (endothelium) different and special in each organ, especially the liver. This knowledge helps us fight a variety of liver diseases, cancer, and hemophilia. As "Cell Therapists", we also use human pluripotent stem cells to model human development and make healthy new endothelium that is a future therapy for liver diseases and Hemophilia A.

1.     Gage BK, Liu JC, Innes BT, MacParland SA, McGilvray ID, Bader GD, Keller GM. Generation of Functional Liver Sinusoidal Endothelial Cells from Human Pluripotent Stem Cell-Derived Venous Angioblasts. Cell Stem Cell. (2020) 27(2): 254-269 e259. Article.

• This study established the core mouse model used in the Gage lab where mouse liver vasculature (LSECs) are replaced by functionally mature hPSC-derived LSECs.
• Exploration of published scRNAseq data of hPSC-LSECs can be found collaboratively here with Dr. Gary Bader (U of Toronto).

2. Gage BK, Merlin S, Olgasi C, Follenzi A, Keller GM. Therapeutic Correction of Hemophilia A by Transplantation of hPSC-derived Liver Sinusoidal Endothelial Cell Progenitors. Cell Rep. (2022) 39(1): 110621. Article.

• This study developed a new higher yield differentiation protocol to make hPSC-derived venous endothelial cells with enhanced liver engraftment potential.
• In collaboration with Dr. Antonia Follenzi (Università, del Piemonte Orientale, Italy), this study also revealed that hPSC-VEC cell therapy can functionally correct severe bleeding phenotypes seen in Hemophilia A mice paving the way for future cell therapy development.

3. Kent GM, Atkins MH, Lung B, Nikitina A, Fernandes IM, Kwan JJ, Andrews TS, MacParland SA, Keller GM, Gage BK. Human liver sinusoidal endothelial cells support the development of functional human pluripotent stem cell-derived Kupffer cells. Cell Rep. (2024) 43 (8): 114629. Article.

• This study used our NSG-LSEC humanized mice as an in vivo source of human M-CSF to facilitate stable human macrophage engraftment in the liver. 
• hPSC-derived yolk sac (primitive and MPP/EMP programs) macrophage progenitors stably engraft NSG-LSEC mice and functionally mature to Kupffer cells with homogenous transcriptional signature (MARCO, TIMD4, FOLR2, IL10 etc.) and robust phagocytotic and erythrophagocytotic capacity.
• Cord blood HSPC progenitors fail to show a MARCO signature but expanded Cord blood-derived macrophage progenitors can generate MARCO Kupffer cells.
• Check out the scRNAseq data including the last mouse liver cell that the human Kupffer cells ate as an ongoing collaboration with the Andrews lab (UWO) here: Data Portal.

*** We are searching for PhD graduate students with experience in cell culture, gene editing and/or bioinformatics to be a part of our CIHR projects.***

If you are interested in joining our group and becoming a new Cell Therapist please send an email to bgage@ohri.ca with a CV, your research interests, and your experience.