Scientists created the first generation of neural stem cells in 2001. In just 10 years, the science went from isolation and production to limited clinical trials today. That is remarkably fast considering the first indication of the existence of neural stem cells in adults wasn’t discovered until the mid-1960s–it took 30 years to isolate the cells. It gives Biomedical Engineering Assistant Professor Randolph Ashton hope that the world soon will see medicine move from treating disease to curing it.
“Things are moving rapidly,” he says. “The time it takes to advance in research has decreased. There are still fundamental questions about how the body and these stem cells work, but science will eventually clear the obstacles and as we do, progression will occur very fast.”
Ashton is among a new generation of scientists and engineers trained to investigate stem cells at the interface of their environment. While previous researchers isolated and developed stem cell technology, Ashton is trained to develop the tools that will allow others to rapidly engineer stem cells for use in therapies to treat and possibly cure brain damage and disease.
“Our generation was educated by smart people in government and policy who sought to train engineers at this interface. It is a political move that is coming to fruition,” Ashton says. “Engineers are now more conversant in stem-cell biology so it should move even faster as we develop the tools to control the biology ex-vivo, in a laboratory environment.”
Ashton earned his bachelor’s degree in chemical engineering from Hampton University and a doctorate in chemical engineering from Rensselaer Polytechnic Institute. In the transition to graduate school, he became interested in investigating the stem cell-material interface. He worked to develop substrates that could influence stem cell differentiation and proliferation.
Using hydrogels of alginate, a seaweed-derived polymer, Ashton and colleagues created scaffolds and observed how the mechanical properties of the material influenced the differentiation and fate of neural stem cells.
“We created hydrogels in which we could culture the neural stem cells,” Ashton says. “If you can control the degradation of the hydrogel, then you can control the proliferative rate of the neural stem cell.”
And, he says, if you can control the mechanical properties of the hydrogel, you can actually influence the stem cells to guide them towards maturing as neurons.
In his postdoctoral research, Ashton began investigating the environmental cues that could influence neural stem cells as they grow on the scaffold. That work continues in his lab at UW-Madison.
The idea is to engineer the stem cell environment outside the body to control the development of higher orders of tissue.
“We want to mimic the endogenous tissue structure so that we can start looking at the actual tissue environment ex vivo, in an artificial environment,” Ashton says. “It’s a lot easier to do this outside an organism rather than inside an organism. All of this is easier said than done, but we are encouraged by recent articles showing the neural cells have innate self organizing properties.”
Currently, he and his team are developing three-dimensional tissue structures which they’ve deemed “alginate Legos.” The idea is to create robust protocols for generating any structure a biologist might want. A researcher could take two pieces of alginate, connect them, modify them, and replicate the anatomical feature desired.
“We’re developing the tools to show we have the control over the stem cell-derived tissue morphology ex vivo,” Ashton says. “We’re creating the intermediate step so that the standard biologist can create the secondary biology. We’re very close to showing we can do it.”