Research redefines proteins' role in the development of spinal sensory cells

September 19, 2017

A recent study led by Samantha Butler at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA has overturned a common belief about how a certain class of proteins in the spinal cord regulate the formation of nervous system cells -- called neurons -- during embryonic development. These findings could one day inform the creation of stem cell-based therapies that restore the sense of touch in paralyzed patients.

The study was published in the journal eLife, which was founded in part by the Howard Hughes Medical Institute.

Bone morphogenetic proteins -- also known as BMPs--play a key role in human development. These proteins, known as growth factors, are signals that stimulate cellular functions such as growth, proliferation, healing and differentiation. In the developing human spinal cord, BMPs are required for the formation of neurons.

Butler's study focused on a class of neurons called sensory interneurons. Sensory interneurons allow a person to react to the environment, such as flinching from pain stimulus, feeling comforted by a reassuring squeeze from a loved one or being able to hold a cup of coffee without thinking about it.

The lack of the sense of touch greatly impacts paralyzed patients. For example, people with paralysis often cannot feel the touch of another person and the inability to feel pain could result in burns from inadvertent contact with a hot surface.

"The understanding of sensory interneuron development has lagged far behind that of another class of neurons--called motor neurons--which control the body's ability to move," said Butler, associate professor of neurobiology, member of the UCLA Broad Stem Cell Research Center and senior author of the study. "This lack in understanding belies the importance of sensation: it is at the core of human experience. Some patients faced with the reality of paralysis place the recovery of the sense of touch above movement."

Previous research had suggested that different concentrations of BMPs correlated with the formation of different categories of sensory interneurons. It was thought that a lower concentration of BMPs would result in one category of sensory interneuron, whereas a higher concentration would result in a different category. Butler's research has found no evidence to support this model.

The research team first manipulated the concentration of BMPs in the spinal cord of a chicken embryo. They found that a specific type of BMP always produces specific categories of sensory interneurons, regardless of the concentration of the BMP. The team found that increasing the concentration of a certain type of BMP will make more of the same kinds of sensory interneuron, but will not create a completely different category of sensory interneuron.

The team then applied these findings to mouse embryonic stem cells in lab dishes. They found that by adding specific types of BMPs, they were able to push the stem cells to create two different categories of spinal sensory interneurons. The types of spinal sensory interneurons created control the sensation of the position of body in space -- called proprioception--as well as body movements that are activated by touch, such as flinching away from a hot surface.

"Central nervous system injuries and diseases are particularly devastating because the brain and spinal cord are unable to regenerate," said Madeline Andrews, a predoctoral student in Butler's lab during the time of this research and first author of the study. "Replacing damaged tissue with sensory interneurons derived from stem cells is a promising therapeutic strategy. Our research, which provides key insights into how sensory interneurons naturally develop, gets us one step closer to that goal."

Butler's team now plans to apply their findings to human stem cells as well as drug testing platforms that target diseased sensory interneurons. They also hope to investigate the feasibility of using sensory interneurons in cellular replacement therapies that may one day restore sensation to paralyzed patients.
The research was supported by a National Institute of Child Health and Human Development T32 training grant (HD060549) in developmental biology, stem cells and regeneration, the California Institute for Regenerative Medicine (RB5-07320) and its Bridges to Research program (TB1-01183), the National Institute of Neurological Disorders and Stroke (NS085097) and a UCLA Broad Stem Cell Research Center-Rose Hills Foundation Training Award.

University of California - Los Angeles Health Sciences

Related Stem Cells Articles from Brightsurf:

SUTD researchers create heart cells from stem cells using 3D printing
SUTD researchers 3D printed a micro-scaled physical device to demonstrate a new level of control in the directed differentiation of stem cells, enhancing the production of cardiomyocytes.

More selective elimination of leukemia stem cells and blood stem cells
Hematopoietic stem cells from a healthy donor can help patients suffering from acute leukemia.

Computer simulations visualize how DNA is recognized to convert cells into stem cells
Researchers of the Hubrecht Institute (KNAW - The Netherlands) and the Max Planck Institute in Münster (Germany) have revealed how an essential protein helps to activate genomic DNA during the conversion of regular adult human cells into stem cells.

First events in stem cells becoming specialized cells needed for organ development
Cell biologists at the University of Toronto shed light on the very first step stem cells go through to turn into the specialized cells that make up organs.

Surprising research result: All immature cells can develop into stem cells
New sensational study conducted at the University of Copenhagen disproves traditional knowledge of stem cell development.

The development of brain stem cells into new nerve cells and why this can lead to cancer
Stem cells are true Jacks-of-all-trades of our bodies, as they can turn into the many different cell types of all organs.

Healthy blood stem cells have as many DNA mutations as leukemic cells
Researchers from the Princess Máxima Center for Pediatric Oncology have shown that the number of mutations in healthy and leukemic blood stem cells does not differ.

New method grows brain cells from stem cells quickly and efficiently
Researchers at Lund University in Sweden have developed a faster method to generate functional brain cells, called astrocytes, from embryonic stem cells.

NUS researchers confine mature cells to turn them into stem cells
Recent research led by Professor G.V. Shivashankar of the Mechanobiology Institute at the National University of Singapore and the FIRC Institute of Molecular Oncology in Italy, has revealed that mature cells can be reprogrammed into re-deployable stem cells without direct genetic modification -- by confining them to a defined geometric space for an extended period of time.

Researchers develop a new method for turning skin cells into pluripotent stem cells
Researchers at the University of Helsinki, Finland, and Karolinska Institutet, Sweden, have for the first time succeeded in converting human skin cells into pluripotent stem cells by activating the cell's own genes.

Read More: Stem Cells News and Stem Cells Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to