Human Sensorimotor Organoids Derived from Stem Cells for Studying Advanced Glycation End Products-Induced Hypersensitization

• Grant number: 24/05640-2
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: December 01, 2024
• End date: November 30, 2025
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Vanessa Olzon Zambelli
• Grantee: Gessica Sabrina de Assis Silva
• Supervisor: Joao Duarte Tavares da Silva Pereira
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Institution abroad: University of Alabama at Birmingham (UAB), United States
• Associated to the scholarship: 22/08417-7 - Role of Advanced Glycation Endproducts on Neuronal Degeneration and their Contribution to the Development of Peripheral Neuropathy, BP.DR

Abstract

Advanced glycation end products (AGEs) are proteins or lipids that irreversibly bindto sugar molecules and are consistently associated with the development of peripheralneuropathy and pain. In fact, sensory neurons gain pro-nociceptive functions whenexposed to AGEs. However, the direct effect of AGEs in neuronal and non-neuronalcells together with neuromuscular junctions is unknown. Organoid cultures derivedfrom multiple human iPSC lines have been a promising model for identifying andcharacterizing motor neurons and skeletal muscle, along with sensory neurons,astrocytes, microglia, and vasculature. Therefore, combining the noxious AGEs withorganoids may prove valuable to understanding the pathophysiological mechanisms ofpainful peripheral neuropathies. Thus, using a cultured human sensorimotor organoidmodel, we aim to establish a cutting-edge model for exploring the single-celltranscriptome of organoids, as well as the sensory neuron functioning upon AGEs-induced sensitization. Together, we form a multidisciplinary team with behavioral painexperts, neuroscientists, and specialists in organoids to further provide translationalapplications for AGEs-induced degenerative diseases.