We’re having a birthday blog carnival for iPS cells! My post is just one of many covering this topic today. Join the party to read what other bloggers think!
Ten years ago, the discovery of induced pluripotent stem (iPS) cells by Shinya Yamanaka overturned a long-standing dogma in cell biology: that adult cells, once committed to a certain lineage, could never go back to being stem cell-like. Since then, the path of a cell has changed from a fixed, one-way street to a two-way highway with multiple interchanges.
Unlike embryonic stem cells, iPS cells are adult cells that have been reprogrammed to a stem cell-like state using a cocktail of factors. This means that they circumvent the ethical issues behind stem cell use. They also open the door to personalized cell therapies that get around the huge problem of immune rejection. We can take a patient’s own skin cells and change them into virtually any other cell type. It’s no wonder Yamanaka won the Nobel Prize just six years later!
So why aren’t we offered a plethora of iPS-based therapies when we have a heart attack or a stroke? Were iPS cells all hype and no substance? Of course not!
The promise of iPS cells hasn’t been fully realized for the same reason cell therapies in general aren’t ubiquitous (yet) – they’re still cells. And there are a lot of hurdles to bringing a cell therapy to the clinic.
They have to survive and integrate
First, we’re still not very good at keeping cells alive after transplantation regardless of the cell source. Cell survival is often less than 1%. Second, survival itself isn’t enough – transplanted cells need to integrate with existing cells and perform their required function, whether that’s sending nerve impulses along the spinal cord or beating like heart muscle. Novel cell delivery vehicles that protect the cells upon transplantation and contain factors to promote survival and integration are slowly improving these numbers.
At the University of Toronto, Professor Molly Shoichet is engineering jello-like materials for improved cell transplantation to the central nervous system, while Professor Milica Radisic builds “gyms” for beating heart cells to make sure they’re in tip top shape.
There has to be enough of them
Next, and partly because of this low cell survival, we need lots of cells for every transplant. I’m talking millions. This usually requires weeks of cell culture in large flasks, bags, or bioreactors. For iPS cells there’s the additional barrier of reprogramming efficiency – not all adult cells become iPS cells.
Improvement in differentiation efficiencies, as well as better methods for large-scale cell culture, will help us get the cell numbers we need, faster. The Keller lab at the University of Toronto is focused on efficiently generating all sorts of different cell types from stem cells.
“It’s our mission… to figure out how to direct these cells to make the cell type we want,” says Professor Gordon Keller.
They have to be safe
Last but not least, getting approval from the FDA or Health Canada for cell therapies is also an arduous process, though that’s not necessarily a bad thing.
“The regulatory pathway is long and expensive; we have to make sure that the cells are safe and of course beneficial to overcoming disease,” says Molly Shoichet.
A cell is a living thing. Unlike a drug that has one fixed structure, a cell can do many things, not all of which are beneficial. Cell populations are also heterogeneous: even if two cells look alike by one measure, they may be different by another. And if the cell population is not pure, how can we predict what they’re going to do in the body? We need to be absolutely certain about what we’re transplanting.
Improved methods for cell sorting can help us reach the purity we need while identification of the most important markers that define a given cell population will help us be sure of what to sort for.
So what’s the verdict on iPS-based cell therapies? Keller thinks we’ll start seeing them within the next 10 years while Shoichet is a little more conservative.
“I’m not sure when, but I am sure it will be.”
For now, let’s not focus on what we don’t have, but rather how far we’ve come. I mean, we can now make your skin cells into brain cells. If that’s not progress, what is?
