Past Winner
2004 NSERC Doctoral Prize

Arindom Sen

Biomedical Engineering

University of Calgary

A Canadian scientist has set the groundwork for the clinical-scale production of neural stem cells. Dr. Arindom Sen has developed methods to grow large quantities of the cells in the lab, and he's shown that these cells are a viable source for transplantation in an animal model of Parkinson's disease.

The finding raises the hope that cultured human stem cells could one day be transplanted into human patients. This would provide a critical alternative to the human fetal tissue presently used in a promising experimental treatment for Parkinson's disease, a degenerative disorder in which a specific group of neural cells die.

"One problem is that it takes neural tissue from several human fetuses to do a single operation. So if you have thousands of people with Parkinson's and you want to treat them in this manner you're going to need hundreds of thousands of fetuses, which for practical and ethical reasons you cannot obtain," says Dr. Sen, a recent University of Calgary Ph.D. recipient and winner of a 2004 NSERC Doctoral Prize – one of Canada's premier awards for new doctoral graduates.

Since the discovery of mammalian neural stem cells in 1992, scientists have been able to grow them in the lab, but only in small quantities for research rather than for clinical applications. Dr. Sen has developed protocols for the large-scale production of the cells.

"It's the difference between someone who brews beer at home in a small container and someone who brews beer in an industrial setting," says Dr. Sen, now an assistant professor of Biomedical Engineering at the University of Calgary, who's equally comfortable in the biologist's lab coat and the engineer's hard hat.

During his master's research, also at Calgary, Dr. Sen developed a new, more effective medium for growing neural stem cells. By improving the growth medium and the environmental conditions, he increased cell density by 300 per cent, and doubled the cell culture life as compared with earlier reported results.

Dr. Sen's doctoral research, carried out in the University of Calgary's Pharmaceutical Production Research Facility (where he's now the Director of Research) with Dr. Leo Behie, established the scale-up protocols needed to produce clinically required quantities of neural stem cells using this improved growth medium.

This involved moving from a petri-dish-sized container currently used by researchers to a one-litre computer-controlled bioreactor. A one-litre bioreactor will support the production of enough human neural stem cells, Dr. Sen estimates, to treat a single patient.

One of the most vexing challenges Dr. Sen overcame was that of controlling the size of cell clusters. Neural stem cells naturally grow in aggregates. However, in an in-vitro suspension, if an aggregate grows too big the cells in the middle die, adversely affecting the entire culture.

"We found that we can control the size of the aggregates by controlling the liquid forces that they're exposed to," says Dr. Sen.

One of the concerns with using stem cells for therapeutic reasons is that they can form cancerous tumours upon implantation. However, there was no indication of this when cells cultured for 60 days were transplanted into animals with Parkinson's-like conditions.

"In fact, what we found is that the cells were able to survive for a long period of time, they were able to integrate into the host brain, and they were able to give rise to functional cells in the brain, which is fantastic," says Dr. Sen, whose research was funded in part by the Stem Cell Network of Centres of Excellence.

He's currently continuing his work with human neural stem cells, and is involved with developing similar scale-up techniques for stem cells isolated from other organs.