Comprehensive Molecular Analysis of Pre- and Postmenopausal Human MammaryCells to Enable Their Optimized Growth as Organoids Ex Vivo - Year two

The goal of this project is to discover new factors essential for maintaining a normal human mammary gland. The approach is togenerate and analyze in depth the protein-encoding RNAs and chromatin states that control their expression in the different types ofcells that constitute the human mammary epithelium and its surrounding stromal cells. This will involve analyses of cells isolated fromdiscarded healthy breast tissue obtained with consent from women undergoing reduction mammoplasties.

Development of a commercial protocol to differentiate human pluripotent stem cells into skeletal muscle progenitor cells (hPSC-SMPCs) with transplantation potential

Recent scientific breakthroughs have led to the development of methods to differentiate human PSCs (hPSCs) into skeletal muscle cells. This has allowed, for the first time, the development of cellular models to study muscle diseases such as Duchenne Muscular Dystrophy and the possibility to utilize these cells for cell therapy applications. However, the reliability, efficiency and prober characterization of cells produced from these differentiation protocols remains a roadblock for their routine utilization by the research community.

Serum Protein and Antibody Interactions with Immunomagnetic Cell Isolation Particles

Immunomagnetic cell isolation particles are widely used to separate cells from complex, biological environments, such as blood, urine, or bone marrow. Cell isolation particles are typically decorated with specialized antibodies to bind to targeted cell surfaces via specific antibody–antigen interactions. These interactions can be disturbed by the presence of serum proteins, which are common constituents of cell isolation buffers to prevent cell aggregation.

Evaluating the health of primary human airway epithelial cell cultures grown at air-liquid interface

There are many ways for scientists to study lung diseases.  One way that scientists try to understand lung disease is by growing and examining lung cells in the lab.  While most cells are grown submerged in special liquid that provides the cells with nutrients, a more sophisticated model is to grow cells in an air liquid interface with the top surface of cells exposed to air and the bottom to the liquid with nutrition.  This more closely mimics the real life situation.  When cells are studied in air liquid interface it is very important to make sure they are not damaged by the experiment un

Baseline parameters for application of human 3-D organoids as an in vitro model for studying neurotropic viral infection

Viruses that infect the brain, such as Zika virus, are a significant threat to public health in Canada since many are poorly understood, and no vaccines or antivirals exist to combat them. We are investigating the use of “mini-brain” organoids derived from human stem cells as a model to study Zika virus infection that mimics the physiology of the human brain. Here, we seek to optimize our methodology for infecting brain organoids with Zika virus.

Pilot-scale preparation of phospholipid-free small unilamellar vesicle formulations with potential in treatment of hepatic diseases

Lipid-based nanoparticular drug formulations are a successful technique to enable targeted treatment. The Canadian company Precision Nanosystems Inc. (PNI) develops the innovative instrument family NanoAssemlr for lipid nanoparticle preparation based on microfluidics. These instruments are fast, easy-to-use and provide a high batch-to-batch reproducibility and quality. Recently, we developed a novel lipid nanoparticle formulation with the unique feature of selective liver targeting, which could only be prepared with NanoAssemlr Benchtop at relatively small scale.

Scaling 3D Microtissue Production Using a Microwell System

Tissue engineering works to replace damaged tissue and organs, and has applications in treating diseases such as diabetes. To improve the performance of tissue engineering treatment and research, our lab has produced the microwell system which creates microtissues in the form of cellular balls. The microwell system has been used used internationally under the brand name AggreWell™, supplied by STEMCELL Technologies and allows researchers to produce enough microtissues to treat diseases in animal models, such as mice.

Development of a commercial protocol to differentiate human pluripotent stem cells into skeletal muscle progenitor cells (hPSC-SMPCs) with transplantation potential

Recent scientific breakthroughs have led to the development of methods to differentiate human PSCs (hPSCs) into skeletal muscle cells. This has allowed, for the first time, the development of cellular models to study muscle diseases such as Duchenne Muscular Dystrophy and the possibility to utilize these cells for cell therapy applications. However, the reliability, efficiency and prober characterization of cells produced from these differentiation protocols remains a roadblock for their routine utilization by the research community.

Testing, evaluation and development of a commercial protocol to differentiate hPSC-derived pancreatic progenitors into insulin-producing ?-cells in 2D monolayers and/or 3D culture systems

The generation of functional ?-cells from human pluripotent stem cells (hPSCs) for cell replacement therapy and disease modeling of diabetes is a strongly investigated area. Recent scientific breakthroughs have enabled derivation of large quantities of human pancreatic ?-like cells in the laboratory, but the protocols are currently not consistent or optimized for cells of various genetic backgrounds. We aim to develop a commercial kit to differentiate hPSCs into ?-cells with reproducible efficiencies between multiple cell lines.

CyTOF-based characterization and isolation of MDSC subsets

Myeloid-derived suppressor cells (MDSC) are an unusual type of blood cell that is able to potently turn off immune responses. These cells are not normally present in healthy individuals, when a tumour is present, MDSC can block clearance of the tumour by the body’s immune defenses. A better understanding of how MDSC shut down tumour clearance would greatly improve the success of cancer treatments. Unfortunately, MDSC are difficult for scientists to study because there is currently no effective method to isolate them in pure form.

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