S5 – Unleashing the Potential of Human Induced Pluripotent Stem Cells in Neuroscience Research

The discovery and application of induced pluripotent stem cells (iPSCs) have revolutionized the field of neuroscience research. iPSCs, derived from adult human cells, possess the remarkable ability to differentiate into various cell types, including neurons. This symposium aims to explore the profound impact of iPSCs in understanding the physiology and pathophysiology of the human brain.
By generating iPSCs from adult human cells (hiPSCs), such as skin or blood cells, researchers can recreate an embryonic-like state and study human brain development and diseases at a cellular level. This approach enables the modeling of a range of neurological disorders, including Parkinson’s disease, Alzheimer’s disease, and autism. iPSCs derived from patients with these disorders or known mutations offer valuable insights into disease progression and the identification of potential treatments.
An exciting frontier in this field is the creation of brain organoids, or “mini-brains,” wherein different cell populations differentiate to mimic the cellular diversity of various brain regions. These three-dimensional structures offer insights into the organizational principles of brain areas, and also to assess neuronal function in a more complex and “realistic” environment.
Both distinguished and mid-career speakers at the symposium will present their latest advances in iPSC research, providing valuable knowledge to colleagues in the region and amplifying its impact. Marilia Zaluar (Universidade Federal do Rio de Janeiro, Brazil) develops human neural models related to opioid tolerance, epilepsy, and viral infections affecting the nervous system. Ana Lis Moyano (CIMETSA, Córdoba, Argentina) will share her findings on how extracellular vesicles shape the development of organoids and disease progression in human-derived neurons from Alzheimer’s patients. Maria Ioannou (University of Alberta, Canada) will share her research connecting lipid alterations in Parkinson’s disease to α-synuclein pathology using iPSC-derived dopaminergic neurons of patients with GBA1 and LRRK2 mutations. Lastly, Thomas Durcan (McGill University, Canada) will showcase an open science platform for collaborative efforts in creating a repository of hiPSCs to gain insights into treating a wide range of neurological diseases.
This symposium marks a pivotal moment for human iPSC research in Argentina, with the goal of fostering collaboration and knowledge exchange among researchers in neuroscience. By bringing together diverse perspectives and regions, we aim to create bridges that will positively impact our research community and ultimately advance our understanding of the human brain.

Studies with human induced-pluripotent stem-cells (hiPSC) and pathogens initially focused on immune cells, since there is a great translational gap between human and murine models regarding inflammation. Fueled by the Zika virus pandemic, these techniques made possible establishing a causal relationship between infection and microcephaly. Moreover, we have looked for an environmental agent to explain why the northeast of Brazil had more microcephaly cases than the rest of the country, and have modeled in vitro what this agent does to neurons. More recently, we used hiPSC-derived cellular and tissular models to investigate SARS-CoV-2 infection in distinct cell types and to search for new treatments to NeuroCOVID. Independent of when the causal agent arose or will arise, modeling infections with human cells will certainly be valuable and complementary to animal models in the comprehension of human and animal infectious diseases, past, present and future.

Marília Zaluar Guimarães
marilia.zaluar@idor.org
Instituto Dor de Pesquisa e Ensino. Rio de Janeiro, Brasil.
https://ppgcm.icb.ufrj.br/marilia-zaluar/

Extracellular vesicles (EVs) play a fundamental role in intercellular communication between different cell types in the central nervous system (CNS). These small nanoparticles transport diverse molecular cargoes, including proteins, RNAs and lipids, which not only can reflect the condition and identity of their parental cell but also elicit changes in recipient cells. EVs are key mediators of CNS functions, facilitating signaling across the blood-brain barrier and CNS-periphery communication under both healthy and pathological conditions. Therefore, EVs are extensively investigated as biomarkers for CNS diseases and in regenerative medicine as an alternative to cell therapy. Stem-cell EVs exhibit a biological activity comparable to cell-based therapies, have less immunogenicity, are easier to manipulate, and do not form teratomas. Our research suggests that EVs produced by neural stem cells may be responsible for the therapeutic effects in CNS injury. Moreover, stem-cell derived EVs can reflect early hallmarks of CNS diseases.

Ana Lis Moyano
ana.moyano@iucbc.edu.ar
CIMETSA, Córdoba, Argentina
https://www.iucbc.edu.ar/cimetsa/vesiculas-extracelulares-y-enfermedades-desmielinizantes.html

Intercellular transmission of α-synuclein contributes to the pathology of Parkinson’s disease. Yet, the mechanisms of α-synuclein spread are not fully understood. Here, we will show how defects in glucosylceramide metabolism induce the shedding of extracellular vesicles loaded with pathogenic α-synuclein fibrils in primary cortical neurons and in iPSC-derived dopaminergic neurons of patients with GBA1 and LRRK2 mutations. These data reveal glucosylceramide as a key player driving α-synuclein transmission in Parkinson’s disease.

Maria S. Ioannou
ioannou@ualberta.ca
University of Alberta, Alberta, Canada
https://www.ualberta.ca/cellbiology/people/faculty/maria-ioannou.html

As Associate Professor within the Montreal Neurological Institute (The Neuro) and McGill University and Director of the Neuro’s Early Drug Discovery Unit (EDDU), my group is focused on the use of human induced pluripotent stem cells (iPSCs) for fundamental and translational discovery projects through partnerships with academia and industry. Founded a decade ago, the group has established a cohort of 150+ iPSCs that have been advanced into different projects within the group and used to generate a wide range of neuronal and glial subtypes, in addition to more advanced 3D brain organoid models. For the talk, I will focus on a number of case studies from the group, describing how the group develops stem cell models within a dish to model a disease on a dish. Examples will include Parkinson’s disease, Leukodystrophies and Fragile X as case studies. This work is funded through research grants from the Michael J Fox Foundation, Brain Canada, CQDM, the Canadian Institute for Health Research, the US Department of Defense (DOD) and the McGill Healthy Brains, Healthy Lives (HBHL) initiative.

Thomas Durcan
thomas.durcan@mcgill.ca
McGill University, Canada
https://www.mcgill.ca/neuro/thomas-durcan-phd