MnDRIVE fellow delving into the sensory side of spinal cord injury

Congratulations to Anne Huntemer-Silveira, a PhD student in the Parr Laboratory, for beginning her MnDRIVE (Minnesota’s Discovery, Research, and InnoVation Economy) Discoveries through Industry Partnerships Fellowship. The one-year fellowship will enable Huntemer-Silveira to continue to move her thesis project forward: Functional Characterization of iPSC-Derived Cell Types for In Vitro Modeling of Spinal Cord Injury and Chronic Pain.

According to MnDRIVE, “In Minnesota, there are over 900 cases of spinal cord injury every year and more than half of these cases result in paralysis of two or more limbs. Upwards of 30,000 Minnesotans seek treatment for chronic pain each year, with many turning to harmful, addictive drugs to help with pain management. Anne's research project lays the foundation for the development of a unique stem cell model that can be used to study sensory circuitry in the spinal cord. She will use an application of molecular and optogenetic approaches as well as inclusion of human dorsal root ganglia. The development of this model has the potential to impact treatment options and will help improve the quality of life for many.”

Working with collaborators
Anne Huntemer-SilveiraHuntemer-Silveira (pictured at left) is mentored during the fellowship by Ann Parr, MD, PhD, of the Neurosurgery Department, whose lab’s research focus is on stem cell transplantation to help treat spinal cord injury. Another member of the research team is Lucy Vulchanova, PhD, from the Neuroscience Department, who studies mechanisms of pain in the dorsal spinal cord. Huntemer-Silveira is also working closely with optogenetics expert Esther Krook-Magnuson, PhD, of the Neuroscience Department, and with Patrick Walsh, CEO; and Vincent Truong, COO, leaders of Anatomic, Inc., a U of M spinoff. Their company is known for its efficient production of different neural cell types from human pluripotent stem cells.

During the fellowship, Huntemer-Silveira will continue working with a couple of other researchers on developing protocols for creating different spinal cord injury populations, specifically those with a dorsal spinal cord injury. “We want to discover the cellular mechanisms behind the treatment strategy for this kind of injury – how it works, why it works,” she said.

Creating a new cell culture
Her project will combine dorsal spinal cord-derived sensory interneurons created by the Parr Lab with a population of primary sensory neurons developed by Anatomic, Inc. “We want to look at how they wire together, how their identities change in a co-culture, and how they form circuits with each other,” said Huntemer-Silveira.

“It’s a one-year fellowship and anything I can get done will be thrilling,” she added. “The really big pie-in-the-sky goal, which will take much more than a year, is using this co-culture system that we set up with our cells and Anatomic’s to figure out how to create a ‘pain in the dish’ model. We’ll have a spinal cord circuit with primary neurons and our dorsal cord sensory neurons. That’s the major setup for spinal cord sensory input.”

Seminal work on this concept done by the Harvard Stem Cell Institute in Boston and reported in Nature Neuroscience, said the pain in a dish model can help “identify why individuals differ in their pain responses or risk developing chronic pain, and make possible the development of improved drugs to treat pain.”

Exploring sensory recovery
The next three years of Huntemer-Silveira’s project will look at transplanting these cells into the injured dorsal spinal cord just as the Parr Lab has done with iPSC-derived ventral and motor neurons. “We’ve seen really good recovery using that process,” said Huntemer-Silveira. “Looking at sensory recovery hasn’t been explored as much. That’s tragic because most people who have spinal cord injury also have debilitating chronic pain or serious loss of sensory perception.”

Her research team is trying to pull in both motor and sensory components. “Everyone cares a lot about the motor components because that’s what you see – people with a spinal cord injury can’t walk,” said Huntemer-Silveira. “But there is a lot more going on that we need to figure out.”


Glossary

Optogenetics: the use of light to control neurons that have been genetically modified to express light-sensitive ion channels.

Human pluripotent stem cells: a type of pluripotent (capable of giving rise to several different cell types) stem cell that can be generated directly from a somatic (related to the body) cell.

iPSC: induced pluripotent stem cell that is derived from skin or blood cells and has been reprogrammed back into an embryonic-like pluripotent state that enables the development of an unlimited source of any type of human cell needed for therapeutic purposes.

Dorsal spinal cord: the dorsal part of the spinal cord that gives rise to sensation and perception of the nervous system. The nerves that originate there innervate different regions of the body.

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