IMPROVING PERSONALIZED MEDICINE THROUGH DISCOVERY OF PAIN MECHANISMS USING PATIENT-DERIVED NEURONS

Leader(s): Steven A. Prescott, MD, PhD; and Michael W. Salter, MD, PhD
Institution(s): The Hospital for Sick Children
Other Members: James Ellis, PhD; and James Whitlock, MD



Why was the study done?
Our sense of touch and pain begins with the activation of sensory neurons (nerves). Those neurons respond to stimulation with short pulses of electricity called spikes, which are relay information to the brain. How we perceive each stimulus depends on the number and patterns of spikes it evokes. If a neuron is injured, it may respond to a touch stimulus with too many spikes, causing touch to be mistakenly felt as pain.

How was the study done?
Our research seeks to understand the injury-induced changes that cause neurons to respond more vigorously than normal. Traditionally this is studied using neurons from rats or mice, but ideally we would study human neurons because each person’s neurons may respond differently to injury, making them more or less susceptible to developing neuropathic (nerve) pain. But unlike a blood sample, neurons cannot be easily collected from a patient. The situation has only recently changed thanks to breakthroughs in stem cell technology that now allow neurons to be created from a specific type of stem cells (known as iPSCs) generated in the lab from easily-collected blood or skin cells.

What were the study results?

We have been working to produce human iPSC-derived neurons. Our recent publication (see link below) describes the generation of many different cell types from iPSCs generated from volunteers in the Personal Genome Project Canada. Based on their extensive genetic characterization, these iPSCs and the sensory neurons derived from them provide a valuable comparison for future testing of patient-specific neurons. 
We continue to study these human neurons to identify what changes cause them to over-react under pathological conditions.
This knowledge will help us understand neuropathic pain and its management.


Recent Updates:

https://www.biorxiv.org/content/10.1101/666560v1.article-info

Recent publication (Hildebrandt et al. 2019) describes the use of induced pluripotent stem cells (iPSC) to generate a variety of different cell types from volunteers of the Personal Genome Project Canada.

Last updated: January 2021


Selected Publications:
  • Hildebrandt MR et al. Precision Health Resource of Control iPSC Lines for Versatile Multilineage Differentiation. Stem Cell Reports. 2019; 13(6): 1126-1141. doi: 10.1016/j.stemcr.2019.11.003.