Stem cells in bite-size pieces
Tackling the huge subject of stem cells is a daunting task, in fact similar to the question about how do you eat an elephant; the solution for both: in bite-size pieces! Below are some of the most succulent ‘bites’ of the latest stem cell research.
How do stem cells work?
After motor neurones are damaged in MND, the body does not have the potential to stimulate the growth of new ones, thus one suggestion for a stem cell therapy is that stem cells may be able to turn themselves into replacement motor neurones.
Queries over motor neurone replacement
Replacing motor neurones in the body brings up many questions. How do we know that the stem cells have turned themselves into motor neurones? How do the new motor neurones know which muscle cell to connect up to? These hurdles were overcome when our bodies were growing their first set of motor neurones- as a foetus growing during our growth and development.
The importance of development biology
Advances in the area of Developmental Biology are extremely important to understand how stem cells are likely to fare, if they are triggered to grow into motor neurones, the second time around. There are many chemical pathways that exist to protect the existing healthy motor neurones that may hinder the progress of new stem cells and the subsequent growth and connection of motor neurones.
Another question mark...
..Over the feasibility of replacing motor neurones in MND is their unusually large size. As they can be up to 1m in length, motor neurones can be up to 100,000 bigger than most other cells in the body. Other logistical questions include the number of stem cells to be given and the best place to give them - always considering the balance of risks vs. benefits as for any new therapy.
Are stem cells susceptible to MND?
Is it beneficial to replace motor neurones, will they also be killed by whatever killed the original motor neurones? The cause of MND on a cellular level is unknown, however there are a number of possible biochemical pathways that may contribute to motor neurone degeneration. As we do not know the cause, it is difficult to know whether new stem cells (or motor neurones) are likely to be affected by the same malfunctioning pathways.
It may be more productive to use the unique properties of stem cells in other ways:
Generating motor neurones in the laboratory
One way to understand what causes motor neurones to die is to study them in isolation in the laboratory. The availability of motor neurones to do this is a problem – it is extremely difficult to obtain human motor neurones or to grow motor neurones isolated from animal models of MND. To overcome this problem scientists are learning how to trigger human and animal-derived stem cells to grow into motor neurones in the laboratory. In 2005 a number of important advances were made in this area, which will allow the MND research to move forward faster:
·Dr Zhang and colleagues in Wisconsin were able to identify the specific chemical ‘cocktail’ that will instruct the human embryonic stem cells (human ESC) to grow into motor neurones.
·In addition to growing human ESC in the laboratory, Korean researcher Dr Hwang has established proof of principle that it is possible to manipulate them so that they are ‘tailor-made’ to match someone’s genetic make up. Dr Hwang's research has now been discredited
·A UK licence was awarded to allow the use of human ESC for MND research. Together with skin cells from people with the rare, familial form of MND, this will allow Profs Shaw and Wilmut to develop the best model for studying motor neurones in MND to date.
Novel therapies
Dr Clive Svendsen and colleagues, based in Wisconsin, are currently investigating the potential of stem cells as a method of drug delivery and as a novel approach to therapy. Recently researchers have shown that motor neurone support cells, known as glial cells, may contribute to the cause of MND, and as such may be a therapeutic target. Dr Svendsen’s early results in animal models of MND have shown that stem cells appear to develop into glial cells and are producing a neurotrophic factor, that the stem cells were genetically engineered to produce. Previous clinical trials of neurotrophic factors in MND were unsuccessful, partially due to their poor delivery.
Res Inf H - Lessons from Neurotrophic Factor clinical trials (118 kb)