Stem Cell-Derived “Spinal Cord-Like” Microtissues Afford Personalized Drug Screening
Amyotrophic lateral sclerosis (ALS) is a fast-progressing neurodegenerative disease with an average survival time of three years and no effective treatments. In ALS, motor neurons in the spinal cord, which are required for muscle contractions, die off, leading to progressive muscle paralysis. The molecular causes of ALS are poorly understood, but neuroinflammation, a process of excessive inflammation fueled by immune cells in the spinal cord, is thought to contribute to motor neuron death in ALS. Reducing neuroinflammation may be a tractable way to treat ALS.
To be able to study ALS-linked neuroinflammation in the lab, the team of Elisa Giacomelli and Lorenz Studer with the Memorial Sloan Kettering Cancer Center, USA, generated “spinal microtissues” containing motor neurons and immune cells from stem cells. Their work was recently published in Stem Cell Reports. Interestingly, spinal microtissues made from ALS patients secreted more inflammatory proteins than microtissues from healthy donors. Further, motor neurons in ALS microtissues died off over time, recreating hallmarks of ALS pathology in the dish. To identify potential new treatments, the researchers tested 190 FDA-approved drugs in these microtissues and found that a specific class of drugs consistently brought the levels of inflammatory proteins in ALS microtissues back to levels measured in healthy tissues. Consequently, motor neuron death was reduced as well. These data suggest that the new microtissues will serve as scalable platforms for high throughput drug screening projects and for studying neuroinflammation in ALS in a patient-specific context.
About Stem Cell Reports
Stem Cell Reports is the open access, peer-reviewed journal of the International Society for Stem Cell Research (ISSCR) for communicating basic discoveries in stem cell research, in addition to translational and clinical studies. Stem Cell Reports focuses on original research with conceptual or practical advances that are of broad interest to stem cell biologists and clinicians.