Who would have thought?
By experimenting with an ingredient in Silly Putty, a popular children’s toy, researchers have improved on the substrate media normally used for growing embryonic stem cells in culture. In addition to a number of other factors, growth of human embryonic stem cells is affected by the texture of the surface on which they are growing.
In the last several years, bio-researchers who work with embryonic stem cells have made enormous progress in studying how these stem cells can be transformed into working spinal cord cells. Generally, this process involves plying the stem cells with chemical signals to cause them to change the pattern of expression of their genes – by doing so, the stem cells will differentiate (i.e. develop) into other types of cells, such as muscle, bone, or nerve. In the study reported on today, the researchers found that the efficiency of this transformation can be enhanced by changing the surface (substrate) on which the cells are grown. This is the first demonstration that physical signals can affect embryonic stem cell development, in addition to chemical signals. The study, performed by a research team led by Jianping Fu of the University of Michigan, was published in Nature Materials on April 13.
The team used a chemical component of Silly Putty called polydimethylsiloxane, to create “carpets” with threads made of microscopic posts on which they proposed to grow stem cells, to improve the process of changing the stem cells into neurons in culture. These carpets have tunable mechanical rigidity, meaning the stiffness of the carpets can be modified by changing the height of the microscopic posts – the shorter the posts, the more rigid they are. The carpets were used as substrates (i.e. surfaces – think of a petri plate) for growing stem cells. The stem cells grown on the taller, softer carpets transformed into neurons much faster and more reliably than cells grown on the stiffer surfaces. Over 23 days, the colonies of new spinal cord cells were larger and more pure than those grown on the more rigid carpets, or on the traditional plates.
In addition to improving on growth strata for generating larger numbers of neurons in culture, Dr. Fu’s team was also able to show that the new motor neurons they generated behaved similarly to neurons naturally present in the human body. Their research also contributed to the understanding of how neurons send chemical messages to the nucleus to respond to mechanical events taking place outside the cell.
Dr. Fu is excited about his results. They indicate a major advance in the search for a better cell culture system, which is necessary to realize the full potential of the clinical applications of embryonic stem cell technology. In particular, Dr. Fu is collaborating with Dr. Eva Feldman at U-M Medical School, who studies amyotrophic lateral sclerosis (ALS, also known as “Lou Gerhig’s Disease). ALS paralyzes its victims, killing motor neurons in the central nervous system. Being able to grow high-yield cultures of highly pure motor neurons will assist researchers who are seeking to study neurological diseases in the laboratory. The researchers hope that useful stem cell therapies will ultimately help patients afflicted with ALS (or other neurological complaints) to grow their own nerve cells. The use of Silly Putty in growing stem cell cultures has led to improvements in the process of cultivating these cells. Hopefully, the results reported on today will translate into clinical applications in the future.
By Laura Prendergast
University of Michigan