“Boning up” on stem cells
Dr. Derrick Rancourt’s innovative stem cell research could help treat people with osteoporosis and other bone conditions.
Story by Tara Narwani/Illustration by Julia Deakin
Newspapers often present biomedical discoveries as promised new medical treatments or even cures. Hype certainly accompanied the discovery of human embryonic stem (hES) cells. hES cells are pluripotent, which means they have the capacity to develop into any other cell type in the human body. This quality led to predictions that hES cells would be used to replace or repair diseased or damaged tissues in patients.
In his lab at the University of Calgary, Dr. Derrick Rancourt has been studying how to use hES cells to produce osteoblasts, cells in our body that make bone. The hope is that “in the future, we could transplant osteoblasts into patients with osteoporosis as a way to help heal fractures,” says Dr. Rancourt. Osteoporosis is a bone-thinning disease that is most commonly diagnosed in the elderly.
To produce osteoblasts, Dr. Rancourt initially grew hES cells on a solid growth medium in Petri plates. When the hES cells were exposed to specific chemicals, they developed into osteoblasts. However, these cells were difficult to harvest from the plates, making it nearly impossible to produce bone for therapeutic purposes. This led Dr. Rancourt and his team to test a novel method for culturing hES cells more efficiently and in larger quantities using a suspension bioreactor (see Cool tools).
Unexpectedly, however, many of the hES cells in the bioreactor failed to develop into osteoblasts. In other words, the hES cells maintained their identity. “We were surprised. Initially, we thought this was disastrous. Our idea of developing a unique bioprocess to produce bone cells was basically in the toilet,” recounts Dr. Rancourt.
Despite the setback, Dr. Rancourt, a self-described applications-driven scientist, saw an opportunity for the bioreactor due to a major new discovery in stem cell biology. A Japanese researcher had engineered a new type of stem cell, called an induced pluripotent stem cell (iPSC), which behaves like an embryonic stem cell. The advantage of iPSCs is that they’re developed from a patient’s own cells. As a result, tissue developed from iPSCs and used for transplantation would significantly reduce tissue rejection, which is a concern with hES cells.
Dr. Rancourt realized that the bioreactor could be a useful technology in the field of tissue banking. Tissue banking involves the storage of frozen biomedical tissue, such as stem cells, so they can be used later. Using the bioreactor, a sufficient quantity of iPSCs could be produced and banked for future use. For example, a patient could have iPSCs made from their own cells for storage in the bank.
The bioreactor presented yet another opportunity for Dr. Rancourt and his team. As often happens in science, a deeper understanding of scientific phenomena can emerge when investigating unexpected results. He realized some property of the bioreactor helped maintained hES cells or iPSCs in their pluripotent state. The bioreactor uses a suspended rotor that constantly mixes a liquid culture of cells, and Dr. Rancourt recently discovered that this constant movement disrupts the location of a protein found at points where cells meet and interact. The movement of this protein appears to play a role in keeping a cell pluripotent.
This discovery makes Dr. Rancourt hopeful that the bioreactor will still be an effective method for producing significant amounts of bone. “Now that we know the pathway that keeps cells pluripotent,” he says, “we’re interested in finding ways to suppress it and see if we can switch the balance in favour of making bone cells.”
Dr. Rancourt continues to look for different ways to apply this technology. In lieu of bone donated from cadavers, which has the risk of transmitting disease to the recipient, the bioreactor could produce bone that is a safer option for transplantation. A large-scale bioreactor could also be used to make bone powder for repairing fractures. “Although this is science fiction today, I’d be interested in knowing whether we could transplant bone-producing cells and use that as a means to build up bone in patients with osteoporosis.”