Sept. 28, 2020

Stem cell breakthrough advances regenerative medicine

McCaig Institute for Bone and Joint Health researchers develop a way to produce large quantities of human pluripotent stem cells in bioreactors

Stem cells, found within tissues of the body, give rise to specific tissues and organs. A special type of cell, called a pluripotent stem cell, is considered a master cell because it can develop into any cell or tissue in the human body.

Pluripotent stem cells are extremely valuable and harbour enormous potential in regenerative medicine because they can be used for many different applications. They offer unique opportunities to advance the development of cell-based therapies, stem cell biobanks and clinical trials. However, there has been one big problem — it’s been difficult for researchers to make the large quantities of these stem cells needed without compromising the cells’ integrity — until now.

A team of McCaig Institute researchers at the Cumming School of Medicine, Schulich School of Engineering and the biomedical engineering graduate program have developed a way to make large quantities of pluripotent stem cells that maintain their effectiveness. The results of this work were published recently in Communications Biology, a Nature publication.

How pluripotent stem cells work

There are two cell states in pluripotent stem cells — naïve and primed. Primed cells are ones that have started to differentiate or direct themselves toward a specific role. Cells that haven’t begun to differentiate are called naïve pluripotent stem cells. They are more recently discovered and often viewed as better for medical use.

“Naïve pluripotent stem cells can be isolated relatively easily in mice but in humans, it’s very difficult,” explains Dr. Derrick Rancourt, PhD, an author on the paper. “As soon as you put them into culture (an environment where cells can grow), they start to differentiate or direct themselves toward a specific role.”

To overcome this hurdle, the research team developed a way to convert primed pluripotent stem cells to a naïve state that is more stable. These naïve cells were then put in stirred suspension bioreactors, a technology used to generate large quantities of cells.

“Conventional primed human pluripotent stem cells do not grow as efficiently in bioreactors as mouse pluripotent stem cells. So, we converted them to naïve stem cells, which are more immature,” explains Dr. Leili Rohani, PhD, a postdoctoral fellow in Rancourt’s lab and the first author of the paper.

Dr. Michael Kallos, PhD, PEng, and his graduate student Breanna Borys, a PhD candidate in the biomedical engineering graduate program, were able to upscale large quantities of the cells in stirred-suspension bioreactors. “The bioreactor helps the naïve stem cells stay in a stable state and allows us to safety and effectively produce the large quantities needed for stem cell therapies,” says Kallos.

Pioneers in stem cell research

Kallos and Rancourt have been working together for 20 years and are pioneers in developing methods for expanding mouse pluripotent stem cells in bioreactors. When they transitioned their work to humans, they initially ran into problems because primed human stem cells don’t expand as readily as mouse cells.

“That’s why this is a critical study — because we were able to show that with the naïve pluripotent stem cells, we can generate a lot more cells, which has tremendous implications for regenerative medicine,” says Rancourt.

Stem cell paper team

Research team, from left: Derrick Rancourt, Leili Rohani, Michael Kalos, Breanna Borys.

Derrick Rancourt is a professor in the departments of Oncology, Biochemistry & Molecular Biology and Medical Genetics, Cumming School of Medicine (CSM), University of Calgary. He is a member of the CSM’s McCaig Institute for Bone and Joint Health, the Alberta Children’s Hospital Research Institute and the Arnie Charbonneau Cancer Institute.

Michael Kallos is a professor in the Department of Chemical and Petroleum Engineering, Schulich School of Engineering, with an adjunct appointment in the Department of Cell Biology and Anatomy in the CSM. He is the associate director of the Pharmaceutical Production Research Facility (PPRF), the director of Biomedical Engineering (BME) Calgary and associate director of the Center for Bioengineering Research and Education (CBRE). He is also a member of the McCaig Institute for Bone and Joint Health.

Leili Rohani is a former postdoctoral fellow in Derrick Rancourt’s lab in the CSM. She is currently a stem cell scientist at the Centre for Heart Lung Innovation (HLI) at the University of British Columbia.

Breanna Borys is a PhD candidate and Vanier Scholar in the biomedical engineering graduate program at the University of Calgary, under the supervision of Michael Kallos at the Pharmaceutical Production Research Facility (PPRF).

The University of Calgary’s multidisciplinary Engineering Solutions for Health: Biomedical Engineering research strategy drives solutions to our most pressing health challenges in disease and injury prevention, diagnosis, and treatments. Our biomedical engineering researchers make a significant impact in our communities by extending lives, improving quality of life, promoting independence, and continuously improving the health system.