Repairing brain function following a stroke is likely to be one of the early applications of therapeutic stem cells. Stem cells are undifferentiated or “generic” cells that have the potential to turn into more specific cell types as needed. There are different degrees of pluripotency (the ability to differentiate into different cell types) depending on the type of stem cell. An embryonic stem cell can theoretically turn into every cell type – grow into an entire person. But there are also many types of stem cell that are already dedicated to being one type of tissue, like bone-marrow stem cells that can turn into various blood components. For stroke repair neuronal stem cells (NSC) are used.

The reason stroke is likely to be an early application is because after stroke the brain attempts to repair itself by recruiting naturally occurring NSC to rebuild lost pathways and restore function. This process is part of what is called neural plasticity (which also includes the brain’s ability to adapt its function to new tasks). So the ability to recruit stem cells for repair functions is already present – adding more NSC should therefore provide more raw material and help the repair process. If a large volume of brain is lost due to stroke it is likely that raw material will be in short supply, and replacing it will aid in repair.

In fact early research with rats has shown that introducing NSC after stroke does improve recovery. But so far it has not improved brain volume (or reduced volume loss) after stroke. The leading hypothesis is that this lack of increased brain volume is due to the fact that the transplanted NSC do not have anything to keep them in place until they have had a chance to be recruited – to make connections and become part of the brain architecture. It’s like having a pile of bricks to repair a collapsed section of building, but having no way to get the bricks to where they need to go.

A possible solution to this problem is to inject the stem cells along with something to serve as a scaffold – something that will keep the NSC in place until they can be used.  Dr Mike Modo and Professor Jack Price who are neurobiologists from the Institute of Psychiatry, and  Professor Kevin Shakesheff who is tissue engineer from the University of Nottingham are working on using microparticles to form a scaffold that can be injected along with NSC. Their work is still preliminary (they are working with rats) so human trials are a ways off, but the concept is very promising.

What this research shows is both the promise and complexity of stem cell therapy. While stem cells are very potent biological agents, it turns out that for most applications you cannot simply inject stem cells into injured tissue and have them make repairs. The application that comes closest to this is using cardiac stem cells to repair heart damage and improve function. This is because the heart is functionally very simple – it’s a pump. In order to function all that is necessary is for the heart muscle cells to contract together – something they do spontaneously. Heart stem cells easily hook up with existing heart cells and start contracting along in rhythm – adding power to the pumping action of the heart. There is some complex wiring in the heart, but if that if faulty it can be fixed with a pacemaker. The brain is more complex than the heart, but luckily the brain possess molecular mechanisms for self-organization. It maps itself to sensory input, for example.

But as we try to get stem cells to do more complex tasks, like grow entire organs, we are finding that one challenge is to get them to organize into a proper 3-dimensional structure. During development from an embryo there are complex chemical signals that help control the developing 3-D structure of organs and the overall body plan.  Plus, everything starts out as a single cell and grows together. The challenge is making (or repairing) an adult-sized organ without waiting 18 years for it to grow from scratch.

The current approach to this problem is to use some kind of scaffolding. This concept is not new to these researchers or this application. Scaffolds have been used to try to get nerves to grow across gaps caused by trauma, for example. Recently researchers were able to grow a new heart from stem cells by using a “decellularized” heart as a scaffold upon which to grow the new heart. Scaffolds are likely to play a significant role in stem cell technology, unless and until we can develop more sophisticated ways to control what stem cells do.

This is a fascinating technology to follow. Stem cells have the potential to usher in a new era of medical interventions – repairing or replacing damaged organs. Currently we can transplant some organs (not the brain, of course) and this is really the only option in many situations. Most other medical interventions for organ failure amount to using drugs or other methods to compensate for organ damage – making the kidney work harder or the heart beat stronger. But such methods have inherent limitations.

At the same time we need to recognize that stem cell therapy is a very new and tricky technology. We have to be patient and let the technology develop. Hopefully we can pick the low-hanging fruit (like heart failure and stroke repair) that will help push the technology forward.